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aaron lerner

Technion Israel Institute of Technology, Medicine, Faculty Member

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A physician and a scientist. over qualified in Pediatrics, Pediatric gastroenterology and nutrition, and adult Gastroenterology, MA in medical management. Extensive experience in administration, Medicine, clinical and scientific research, teaching, and public services. Author of 350, peer-reviewed articles, more than 100 of them in the last 5 years. Active scientifically and clinically and trying to enjoy life.....
Address: Germany and Israel

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Fortis Escorts Heart Institute

Dr. Mohannad M . A . Khader

Arab American University

The University of Sheffield

Annelise Barron

Stanford University

Selcuk University (Selçuk Üniversitesi)

Olubunmi Ogunrin

University of Benin

International Journal of Celiac Disease

Independent Researcher

Monica Ballarino

Università degli Studi "La Sapienza" di Roma

Ege University

Dr. Rohan Malik MD, PDCC, DM

All India Institute of Medical Sciences, New Delhi

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Papers by aaron lerner

Infantile-onset inflammatory bowel disease has variable long-term outcomes

Frontiers in Pediatrics, Mar 1, 2023

Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed ... more Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study. Methods: Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded. Results: Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection. Conclusion: The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis.

Sjögren's Syndrome Associated with Celiac Disease: A Systematic Review

BACKGROUND Autoimmune diseases tend to run in families and the affected persons are prone to addi... more BACKGROUND Autoimmune diseases tend to run in families and the affected persons are prone to additional autoimmune conditions. This is the case for celiac disease (CD) and Sjögren's syndrome (SS). The objectives of this work were to describe a patient with both diseases and to analyze the clinical, therapeutic and evolutionary characteristics of published patients with SS associated with CD. MATERIALS AND METHODS A systematic review of articles published in PubMed, MEDLINE, LILACS and SciELO, dating from 1966 to May 2020, was conducted, using the following search words: Sjögren's syndrome, celiac disease. Only English, German and French publications were considered. RESULTS Only 16 studies with 31 patients with SS associated CD were depicted. Adding the present case would mount the total to 17 studies, describing 32 patients. There are 6 observational studies and 10 case reports. In relation to demographics, age varied from 10 to 73 years old, with a median of 45 years and the great majority were female (21/32 patients). Sjögren's syndrome preceded CD manifestations in 7 studies, CD was the first presentation in 6 articles and simultaneous diseases was observed in 4 reports. Time elapsed between the two diseases varied from 2 to 33 years. Autoantibodies related to SS showed that anti-Ro and anti-La were positive in 8/17, while CD-related antibodies were positive in 12/17 studies. Regarding therapy, the majority received a gluten-free diet as CD therapy (13/17 studies). Glucocorticoid was prescribed in 6/17 studies and hydroxychloroquine in 4/17. When described, all studies demonstrated improvement of CD manifestations and 7/17 improved SS symptoms.

SARS-CoV-2 Gut-Targeted Epitopes: Sequence Similarity and Cross-Reactivity Join Together for Molecular Mimicry

Biomedicines

The gastrointestinal tract can be heavily infected by SARS-CoV-2. Being an auto-immunogenic virus... more The gastrointestinal tract can be heavily infected by SARS-CoV-2. Being an auto-immunogenic virus, SARS-CoV-2 represents an environmental factor that might play a role in gut-associated autoimmune diseases. However, molecular mimicry between the virus and the intestinal epitopes is under-investigated. The present study aims to elucidate sequence similarity between viral antigens and human enteric sequences, based on known cross-reactivity. SARS-CoV-2 epitopes that cross-react with human gut antigens were explored, and sequence alignment was performed against self-antigens implicated in enteric autoimmune conditions. Experimental SARS-CoV-2 epitopes were aggregated from the Immune Epitope Database (IEDB), while enteric antigens were obtained from the UniProt Knowledgebase. A Pairwise Local Alignment tool, EMBOSS Matcher, was employed for the similarity search. Sequence similarity and targeted cross-reactivity were depicted between 10 pairs of immunoreactive epitopes. Similar pairs we...

Cross-reactivity and sequence similarity between microbial transglutaminase and human tissue antigens

Scientific Reports, Oct 15, 2023

Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additi... more Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additive to glue processed nutrients. As a result, new immunogenic epitopes are generated that might drive autoimmunity. Presently, its contribution to autoimmunity through epitope similarity and crossreactivity was investigated. Emboss Matcher was used to perform sequence alignment between mTG and various antigens implicated in many autoimmune diseases. Monoclonal and polyclonal antibodies made specifically against mTG were applied to 77 different human tissue antigens using ELISA. Six antigens were detected to share significant homology with mTG immunogenic sequences, representing major targets of common autoimmune conditions. Polyclonal antibody to mTG reacted significantly with 17 out of 77 tissue antigens. This reaction was most pronounced with mitochondrial M2, ANA, and extractable nuclear antigens. The results indicate that sequence similarity and crossreactivity between mTG and various tissue antigens are possible, supporting the relationship between mTG and the development of autoimmune disorders 150W. Abbreviations ADs Autoimmune diseases ASIA Autoimmune/inflammatory syndrome induced by adjuvants GIT Gastrointestinal tract mTG Microbial transglutaminase tTG Tissue transglutaminase CD Celiac disease AAs Amino acids OD Optical density Genetic predisposition is pivotal for autoimmune diseases (ADs) development, but environmental factors are necessary for their clinical evolvement 1-4. Pending on their association with various ADs, they include: hygiene and diet 5 , food processed additives 6-9 , trace elements 10 , enteric microbial peptides 11 , multiple infectious agents 3,12-15 , various vaccines 16,17 , toxic agents or food products 4 and recently the checkpoint inhibitors 18,19. In fact, many of those environmental factors were cited as part of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 1,20,21. Zooming into the gastrointestinal tract (GIT), many of the above-mentioned environmental factors inhabit the enteric lumen and are associated with local or peripheral ADs 3-13,22. Many processes were described to operate in the human GIT driving gut-originated autoimmunity. The most reported one is increased gut permeability resulting in leaky gut syndrome 6,23-25. Among others are posttranslational modification of naïve proteins 26 , dysbiosis and its harmful mobilome 23,27 , horizontal gene transfer 28 , or many immunogenic nutritional compounds, such as gluten 4,6-9,22,27. All those enteric events irradiate peripherally and might induce systemic autoimmunity 29. Indeed, some of those luminal events are blamed to increase the worldwide incidence of ADs 23,30. Among the various mechanisms that drive autoimmunity, molecular mimicry is the most reported 11,16,31,32. Actually, SARS-CoV-2-associated autoimmunity is suggested to operate through molecular mimicry with self-epitopes 33,34 .

Sjögren Syndrome Associated with Protein-Losing Enteropathy: Case-Based Review

Anais do Congresso Brasileiro de Reumatologia 2020, 2021

BACKGROUND The association between Sjögren's syndrome (SS) and protein-losing enteropathy (PLE) w... more BACKGROUND The association between Sjögren's syndrome (SS) and protein-losing enteropathy (PLE) was scarcely reported. The objectives were to analyze the clinical, therapeutic and outcome characteristics of patients with SS and PLE and also to delineate the potential mechanisms and pathways connecting the gut to SS targeted organ pathology.

370 Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis

Journal of Cystic Fibrosis, 2007

Aim: Assessing functional CFTR activity using nasal potential difference measurement is becoming ... more Aim: Assessing functional CFTR activity using nasal potential difference measurement is becoming an integral component of CF diagnosis in non-classical presentations. We present our experience of an alternative method of assessing functional CFTR activity, which involves intestinal current measurement (ICM) of rectal biopsies, thereby removing the age-limitation from this useful diagnostic aid. Methods: Rectal biopsies were taken from 3 sets of patients: known CF, controls, and suspected CF. This last group included patients with a mean age 3.4±3 years, who were undergoing investigation for a variety of symptoms including recurrent pneumonia, unexplained bronchiectasis, chronic diarrhea and failure to thrive. ICMs were then performed using standard protocols by mounting the rectal biopsy in an Ussing chamber and sequentially adding secretagogues while recording current changes. Results: Comparing the ICMs of the known CF group and the controls revealed a significant difference on addition of the chloride channel activators: Carbachol (p < 0.0001), histamine (p < 0.0001) and cAMP + forskolin (p = 0.003). 7/22 resembled the CF group and 15/22 the control group. There was no difference in sweat tests between these groups. Conclusion: ICM tests may be useful to differentiate between CF and non-CF patients, in particular in those young patients with atypical presentations, in whom performing nasal PD is impractical. Larger studies are needed to confirm these results.

Autoimmunity in celiac disease: Extra-intestinal manifestations

Autoimmunity Reviews, 2019

Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetical... more Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetically susceptible individuals evoked by multiple environmental factors. The pathological luminal intricate eco-events produce multiple signals that irradiate the entire body, resulting in a plethora of extra-intestinal manifestations. Nutrients, dysbiosis, dysbiotic components and their mobilome, post-translational modification of naive proteins, inter-enterocyte's tight junction dysfunction resulting in a leaky gut, microbial lateral genetic transfer of virulent genes, the sensing network of the enteric nervous systems and the ensuing pro-inflammatory messengers are mutually orchestrating the autoimmune interplay. Genetic-environmental-luminal eventsmucosal changes are driving centrifugally the remote organs autoimmunity, establishing extra-intestinal multi organ injury. Exploring the underlying intestinal eco-events, the sensing and the delivery pathways and mechanisms that induce the peripheral tissues' damages

Nonresponsive Celiac Disease Treated with a Unique Functional Medical Approach

by Tom O'Bryan and aaron lerner

International Journal of Celiac Disease. , 2021

A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short statu... more A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short stature, and failure to thrive, presented to this Functional Medicine practitioner because he had exceedingly high tissue transglutaminase (tTG) antibodies and poor growth, despite 10 months on a meticulous gluten-free diet (GFD). Immunological testing showed elevated antibody production against multiple peptides of wheat, food antigens, intestinal barrier dysfunction, lipopolysaccharide (LPS) antibodies, and polyreactive autoimmune reactions. An elimination diet, nutraceutical protocols to modulate the microbiome, address intestinal permeability, lower inflammation, and remove underlying bacterial infection were initiated. Global anti-inflammatory lifestyle modifications were recommended. Within 3 months of treatment, the patient's tTG antibodies decreased by 14% for the first time since strict gluten elimination. Within 15 months, tTG IgG antibodies were nearly normal at 1.61 (0.03-1.60, ELISA Index). Test results improved dramatically in tandem with clinical progress. On a GFD and after initiating and maintaining these dietary and lifestyle changes, he gained 12 inches and 40 pounds. To our knowledge, this is the first published case of complete reversal of NRCD and failure to thrive by addressing endotoxin and lifestyle outside of a GFD.

Pitfall in Diagnosis of Crohnʼs Disease in a Cystic Fibrosis Patient

Journal of Pediatric Gastroenterology and Nutrition, Apr 1, 1991

Cystic Fibrosis Transmembrane Conductance Regulator Ion Channel Function Testing in Recurrent Acute Pancreatitis

Journal of Clinical Gastroenterology, Aug 1, 2008

ABSTRACT To understand the relationship between acute recurrent pancreatitis and cystic fibrosis ... more ABSTRACT To understand the relationship between acute recurrent pancreatitis and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. An emerging number of patients present with a nonclassic phenotype of cystic fibrosis (CF) with partial features or single-organ disease only. The association between the phenotype of recurrent pancreatitis CFTR dysfunction is unclear. Patients with idiopathic recurrent pancreatitis were referred for electrophysiologic investigation. Thirty-three patients (18 males) aged 20+/-12 years with recurrent pancreatitis were studied. Three patients had mild asthma and 1 patient had mild ulcerative colitis. There was no family history of CF. All patients had normal imaging of the pancreatic duct by endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. No patient was pancreatic insufficient. Mean sweat chloride values were 41+/-14 meq/L (range: 18 to 64). Nasal potential difference (NPD) measurement was pathologic in 7 patients. Mean basal potential difference in these 7 patients was -33+/-13 mV and there was an abnormal response to chloride-free and isoproterenol solutions. There was no difference in sweat chloride concentration between the 2 groups. Mutation analysis revealed W1282X/5T, D1152H/5T, and W1282X/- in 3 patients with abnormal NPD and 1 W1282X allele was found in 1 patient with normal NPD. In this series, 21% of patients with recurrent pancreatitis have abnormalities of CFTR function. Patients presenting with recurrent, &quot;idiopathic&quot; pancreatitis require CFTR function testing.

Pediatric Crohn's Disease and Growth Retardation: The Role of Genotype, Phenotype, and Disease Severity

Pediatrics, Nov 1, 2004

Background. Delayed growth is a well-established feature of pediatric Crohn's disease. Severa... more Background. Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity.Methods. Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed.Results. NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively).Conclusions. Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.

Neurological Manifestations of Celiac Disease in Children and Adults

Celiac disease (CD) is a common, life-long, autoimmune condition, affecting the small intestine o... more Celiac disease (CD) is a common, life-long, autoimmune condition, affecting the small intestine of genetically susceptible individuals. The classical clinical picture is disappearing as awareness progresses and the extra-intestinal presentation is emerging. Skin, endocrine, hepatic, skeletal, hematological, gynecological, infertility, dental, and behavioral abnormalities are emerging. Among the new growing domains is the extra-intestinal presentation of CD affecting the peripheral and central neurological systems. This review highlights neurological presentations in these patients, focusing on the clinical signs/symptoms in the pediatric and the adult age group, separately.

Is Enzyme Supplementation Effective Strategy to Reduce the Burden of Gluten Free Diet in Celiac Disease

International Journal of Celiac Disease, 2016

Several strategies have been considered for enzymatic detoxification of dietary gluten and to red... more Several strategies have been considered for enzymatic detoxification of dietary gluten and to reduce immunogenisity of gliadin peptides. An enzymatic therapy using enterically coated tablets containing caricain (Gluteguard), originated from a papaya, on celiac disease patients challenged with gluten was reported. Glut guard was able to protect these patients from adverse symptoms being induced by gluten challenge. The advantages of the fruit originated preparation are: it does not contain living microbes or bacterial purified or engineered products. It can be considered as a preventive therapy and further step in the future therapeutical strategy race for the celiac affected population benefits.

The Underdiagnosed Enemy: Africa Goes Celiac?

International Journal of Celiac Disease, 2019

Celiac disease incidence is continuously increasing worldwide and in Africa, where a clear North ... more Celiac disease incidence is continuously increasing worldwide and in Africa, where a clear North to South gradient is apparent. At least in the Maghreb region, the disease features resemble its European neighbors, but some aspects are completely different. The present review highlights the underdiagnosis and the inadequate nutritional therapy for celiac disease patients and summarizes the local special circumstances that should be address to coop with the contemporary load and future burden of the disease.

The Jigsaw Puzzle of Breast Feeding and Celiac Disease

International Journal of Celiac Disease, 2016

The puzzle of breast feeding effects on celiac disease development is complicated and despite num... more The puzzle of breast feeding effects on celiac disease development is complicated and despite numerous studies, remains unresolved. Several prospective or retrospective observational studies on the topic were reported, with contradictory results. The geoepidemiology teaches us that celiac disease incidence, in the west, is increasing, while breast feeding is decreasing, going along with the protective effect of mother’s milk. But, human milk and gluten are only two in the growing list of environmental factors that affect celiac disease induction or behavior. The recent increased knowledge on gluten side effects in non-celiac populations and the fact that human milk contains gluten peptides, further complicate the breast milk-gluten-celiac disease cross-talks. Latest studies revealed that breast feeding, whether exclusive or in combination with formula intake, did not reduce the risk of CD development. More so, recent publications concluded that timing of introduction of gluten to in...

The Gut-gut Axis: Cohabitation of Celiac, Crohn's Disease and IgA Deficiency

International Journal of Celiac Disease, 2016

An adult patient with IgA deficiency, celiac and Crohn’s disease is described. In addition to the... more An adult patient with IgA deficiency, celiac and Crohn’s disease is described. In addition to the rare association, he developed an unusual proximal Crohn’s disease. Unbalanced microbiome, increased intestinal permeability, susceptibility to infections that might initiate post translational modification of naive protein and the genetic background, are shared between the three entities. It is speculated that the IgA immune deficiency and its consequences are the early factors that set the stage for the progression of the other two diseases. Based on recent knowledge, special nutritional therapies should be considered, in addition to the gluten free diet.

Deamidated Gliadin Peptide Antibodies in Celiac Disease: A Diagnostic Driver or just along for the Ride?

International Journal of Celiac Disease, 2019

Anti deamidated gliadin peptides antibodies are considered as celiac disease associated diagnosti... more Anti deamidated gliadin peptides antibodies are considered as celiac disease associated diagnostic antibodies. They are in clinical use for almost the last two decades. In the first decade they were preferentially used in early childhood, in face of IgA deficiency and occasionally recommended as the prime serological marker, outperforming the anti-tissue transglutaminase autoantibody. Notably, they were recommended in combination with the tissue transglutaminase as enhancer of the diagnostic performances. No more, the circle turned over. In the second decade (2012-2019), most of the studies limited and criticized their past published advantages. They suggested that deamidated gliadin peptides antibodies do not have any advantage over anti-tissue transglutaminase autoantibodies in terms of early childhood, IgA deficiency, diagnostic performances and when both antibodies are combined. It seems that the deamidated gliadin peptide are losing their place in the celiac disease algorithmic...

[The Influence of Gluten on the Sharpness of Vision]

Harefuah, 2020

INTRODUCTION An eighty five old male was diagnosed with celiac disease. Six months before the dia... more INTRODUCTION An eighty five old male was diagnosed with celiac disease. Six months before the diagnosis he complained of difficulties in his sight. In an optimetrical examination a decline in sharpness of sight was found: Right (R) - 6/19, Left (L) - 6/12. Following a few months of a gluten-free diet his situation improved and the signs of celiac disease disappeared. The sharpness of sight was re-examined and good improvement was found: L - 6/9, R - 6/12. This means that gluten might influence the sharpness of sight.

Nonresponsive Celiac Disease Treated with a Unique Functional Medical Approach

International Journal of Celiac Disease, 2021

A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short statu... more A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short stature, and failure to thrive, presented to this Functional Medicine practitioner because he had exceedingly high tissue transglutaminase (tTG) antibodies and poor growth, despite 10 months on a meticulous gluten-free diet (GFD). Immunological testing showed elevated antibody production against multiple peptides of wheat, food antigens, intestinal barrier dysfunction, lipopolysaccharide (LPS) antibodies, and polyreactive autoimmune reactions. An elimination diet, nutraceutical protocols to modulate the microbiome, address intestinal permeability, lower inflammation, and remove underlying bacterial infection were initiated. Global anti-inflammatory lifestyle modifications were recommended. Within 3 months of treatment, the patient's tTG antibodies decreased by 14% for the first time since strict gluten elimination. Within 15 months, tTG IgG antibodies were nearly normal at 1.61 (0.03-1.60, ELISA Index). Test results improved dramatically in tandem with clinical progress. On a GFD and after initiating and maintaining these dietary and lifestyle changes, he gained 12 inches and 40 pounds. To our knowledge, this is the first published case of complete reversal of NRCD and failure to thrive by addressing endotoxin and lifestyle outside of a GFD.

Candida albicans in celiac disease: A wolf in sheep’s clothing

Autoimmunity Reviews, 2020

The purpose of this study was to evaluate the cytotoxic effects of commercially available root ca... more The purpose of this study was to evaluate the cytotoxic effects of commercially available root canal sealers [Sealite Ultra (SU), Tubli-Seal (TS), Tubli-Seal EWT (TS-EWT), Pulp Canal Sealer (PCS), Pulp Canal Sealer EWT (PCS-EWT), Endomethasone N (En N), and Apexit Plus (AP)] on L929 cells by using MTT assay. After incubation with each sealer's extract at 37°C in a humidified air atmosphere containing 5% CO 2 for 24 h, MTT (5 mg/mL) in saline was added into each well and further incubated at 37°C for 4 h. Formazan precipitate was dissolved in a buffer containing 23% sodium dodecyl sulfate and 50% N,N-dimethylformamide (pH 4.7). Optical densities of dissolved formazan were read using a microplate spectrophotometer. AP, TS, and TS-EWT showed no cytotoxicity at any dilution tested. Other sealers exhibited some degree of cytotoxicity at the 1/4 and 1/2 dilutions. PCS-EWT and SU exerted more potent cytotoxicity at 1/2 dilution than the other sealers.

Infantile-onset inflammatory bowel disease has variable long-term outcomes

Frontiers in Pediatrics, Mar 1, 2023

Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed ... more Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study. Methods: Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded. Results: Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection. Conclusion: The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis.

Sjögren's Syndrome Associated with Celiac Disease: A Systematic Review

BACKGROUND Autoimmune diseases tend to run in families and the affected persons are prone to addi... more BACKGROUND Autoimmune diseases tend to run in families and the affected persons are prone to additional autoimmune conditions. This is the case for celiac disease (CD) and Sjögren's syndrome (SS). The objectives of this work were to describe a patient with both diseases and to analyze the clinical, therapeutic and evolutionary characteristics of published patients with SS associated with CD. MATERIALS AND METHODS A systematic review of articles published in PubMed, MEDLINE, LILACS and SciELO, dating from 1966 to May 2020, was conducted, using the following search words: Sjögren's syndrome, celiac disease. Only English, German and French publications were considered. RESULTS Only 16 studies with 31 patients with SS associated CD were depicted. Adding the present case would mount the total to 17 studies, describing 32 patients. There are 6 observational studies and 10 case reports. In relation to demographics, age varied from 10 to 73 years old, with a median of 45 years and the great majority were female (21/32 patients). Sjögren's syndrome preceded CD manifestations in 7 studies, CD was the first presentation in 6 articles and simultaneous diseases was observed in 4 reports. Time elapsed between the two diseases varied from 2 to 33 years. Autoantibodies related to SS showed that anti-Ro and anti-La were positive in 8/17, while CD-related antibodies were positive in 12/17 studies. Regarding therapy, the majority received a gluten-free diet as CD therapy (13/17 studies). Glucocorticoid was prescribed in 6/17 studies and hydroxychloroquine in 4/17. When described, all studies demonstrated improvement of CD manifestations and 7/17 improved SS symptoms.

SARS-CoV-2 Gut-Targeted Epitopes: Sequence Similarity and Cross-Reactivity Join Together for Molecular Mimicry

Biomedicines

The gastrointestinal tract can be heavily infected by SARS-CoV-2. Being an auto-immunogenic virus... more The gastrointestinal tract can be heavily infected by SARS-CoV-2. Being an auto-immunogenic virus, SARS-CoV-2 represents an environmental factor that might play a role in gut-associated autoimmune diseases. However, molecular mimicry between the virus and the intestinal epitopes is under-investigated. The present study aims to elucidate sequence similarity between viral antigens and human enteric sequences, based on known cross-reactivity. SARS-CoV-2 epitopes that cross-react with human gut antigens were explored, and sequence alignment was performed against self-antigens implicated in enteric autoimmune conditions. Experimental SARS-CoV-2 epitopes were aggregated from the Immune Epitope Database (IEDB), while enteric antigens were obtained from the UniProt Knowledgebase. A Pairwise Local Alignment tool, EMBOSS Matcher, was employed for the similarity search. Sequence similarity and targeted cross-reactivity were depicted between 10 pairs of immunoreactive epitopes. Similar pairs we...

Cross-reactivity and sequence similarity between microbial transglutaminase and human tissue antigens

Scientific Reports, Oct 15, 2023

Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additi... more Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additive to glue processed nutrients. As a result, new immunogenic epitopes are generated that might drive autoimmunity. Presently, its contribution to autoimmunity through epitope similarity and crossreactivity was investigated. Emboss Matcher was used to perform sequence alignment between mTG and various antigens implicated in many autoimmune diseases. Monoclonal and polyclonal antibodies made specifically against mTG were applied to 77 different human tissue antigens using ELISA. Six antigens were detected to share significant homology with mTG immunogenic sequences, representing major targets of common autoimmune conditions. Polyclonal antibody to mTG reacted significantly with 17 out of 77 tissue antigens. This reaction was most pronounced with mitochondrial M2, ANA, and extractable nuclear antigens. The results indicate that sequence similarity and crossreactivity between mTG and various tissue antigens are possible, supporting the relationship between mTG and the development of autoimmune disorders 150W. Abbreviations ADs Autoimmune diseases ASIA Autoimmune/inflammatory syndrome induced by adjuvants GIT Gastrointestinal tract mTG Microbial transglutaminase tTG Tissue transglutaminase CD Celiac disease AAs Amino acids OD Optical density Genetic predisposition is pivotal for autoimmune diseases (ADs) development, but environmental factors are necessary for their clinical evolvement 1-4. Pending on their association with various ADs, they include: hygiene and diet 5 , food processed additives 6-9 , trace elements 10 , enteric microbial peptides 11 , multiple infectious agents 3,12-15 , various vaccines 16,17 , toxic agents or food products 4 and recently the checkpoint inhibitors 18,19. In fact, many of those environmental factors were cited as part of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 1,20,21. Zooming into the gastrointestinal tract (GIT), many of the above-mentioned environmental factors inhabit the enteric lumen and are associated with local or peripheral ADs 3-13,22. Many processes were described to operate in the human GIT driving gut-originated autoimmunity. The most reported one is increased gut permeability resulting in leaky gut syndrome 6,23-25. Among others are posttranslational modification of naïve proteins 26 , dysbiosis and its harmful mobilome 23,27 , horizontal gene transfer 28 , or many immunogenic nutritional compounds, such as gluten 4,6-9,22,27. All those enteric events irradiate peripherally and might induce systemic autoimmunity 29. Indeed, some of those luminal events are blamed to increase the worldwide incidence of ADs 23,30. Among the various mechanisms that drive autoimmunity, molecular mimicry is the most reported 11,16,31,32. Actually, SARS-CoV-2-associated autoimmunity is suggested to operate through molecular mimicry with self-epitopes 33,34 .

Sjögren Syndrome Associated with Protein-Losing Enteropathy: Case-Based Review

Anais do Congresso Brasileiro de Reumatologia 2020, 2021

BACKGROUND The association between Sjögren's syndrome (SS) and protein-losing enteropathy (PLE) w... more BACKGROUND The association between Sjögren's syndrome (SS) and protein-losing enteropathy (PLE) was scarcely reported. The objectives were to analyze the clinical, therapeutic and outcome characteristics of patients with SS and PLE and also to delineate the potential mechanisms and pathways connecting the gut to SS targeted organ pathology.

370 Cystic fibrosis transmembrane conductance regulator ion channel function testing in recurrent acute pancreatitis

Journal of Cystic Fibrosis, 2007

Aim: Assessing functional CFTR activity using nasal potential difference measurement is becoming ... more Aim: Assessing functional CFTR activity using nasal potential difference measurement is becoming an integral component of CF diagnosis in non-classical presentations. We present our experience of an alternative method of assessing functional CFTR activity, which involves intestinal current measurement (ICM) of rectal biopsies, thereby removing the age-limitation from this useful diagnostic aid. Methods: Rectal biopsies were taken from 3 sets of patients: known CF, controls, and suspected CF. This last group included patients with a mean age 3.4±3 years, who were undergoing investigation for a variety of symptoms including recurrent pneumonia, unexplained bronchiectasis, chronic diarrhea and failure to thrive. ICMs were then performed using standard protocols by mounting the rectal biopsy in an Ussing chamber and sequentially adding secretagogues while recording current changes. Results: Comparing the ICMs of the known CF group and the controls revealed a significant difference on addition of the chloride channel activators: Carbachol (p < 0.0001), histamine (p < 0.0001) and cAMP + forskolin (p = 0.003). 7/22 resembled the CF group and 15/22 the control group. There was no difference in sweat tests between these groups. Conclusion: ICM tests may be useful to differentiate between CF and non-CF patients, in particular in those young patients with atypical presentations, in whom performing nasal PD is impractical. Larger studies are needed to confirm these results.

Autoimmunity in celiac disease: Extra-intestinal manifestations

Autoimmunity Reviews, 2019

Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetical... more Celiac disease is an autoimmune condition of the small intestine caused by prolamins in genetically susceptible individuals evoked by multiple environmental factors. The pathological luminal intricate eco-events produce multiple signals that irradiate the entire body, resulting in a plethora of extra-intestinal manifestations. Nutrients, dysbiosis, dysbiotic components and their mobilome, post-translational modification of naive proteins, inter-enterocyte's tight junction dysfunction resulting in a leaky gut, microbial lateral genetic transfer of virulent genes, the sensing network of the enteric nervous systems and the ensuing pro-inflammatory messengers are mutually orchestrating the autoimmune interplay. Genetic-environmental-luminal eventsmucosal changes are driving centrifugally the remote organs autoimmunity, establishing extra-intestinal multi organ injury. Exploring the underlying intestinal eco-events, the sensing and the delivery pathways and mechanisms that induce the peripheral tissues' damages

Nonresponsive Celiac Disease Treated with a Unique Functional Medical Approach

by Tom O'Bryan and aaron lerner

International Journal of Celiac Disease. , 2021

A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short statu... more A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short stature, and failure to thrive, presented to this Functional Medicine practitioner because he had exceedingly high tissue transglutaminase (tTG) antibodies and poor growth, despite 10 months on a meticulous gluten-free diet (GFD). Immunological testing showed elevated antibody production against multiple peptides of wheat, food antigens, intestinal barrier dysfunction, lipopolysaccharide (LPS) antibodies, and polyreactive autoimmune reactions. An elimination diet, nutraceutical protocols to modulate the microbiome, address intestinal permeability, lower inflammation, and remove underlying bacterial infection were initiated. Global anti-inflammatory lifestyle modifications were recommended. Within 3 months of treatment, the patient's tTG antibodies decreased by 14% for the first time since strict gluten elimination. Within 15 months, tTG IgG antibodies were nearly normal at 1.61 (0.03-1.60, ELISA Index). Test results improved dramatically in tandem with clinical progress. On a GFD and after initiating and maintaining these dietary and lifestyle changes, he gained 12 inches and 40 pounds. To our knowledge, this is the first published case of complete reversal of NRCD and failure to thrive by addressing endotoxin and lifestyle outside of a GFD.

Pitfall in Diagnosis of Crohnʼs Disease in a Cystic Fibrosis Patient

Journal of Pediatric Gastroenterology and Nutrition, Apr 1, 1991

Cystic Fibrosis Transmembrane Conductance Regulator Ion Channel Function Testing in Recurrent Acute Pancreatitis

Journal of Clinical Gastroenterology, Aug 1, 2008

ABSTRACT To understand the relationship between acute recurrent pancreatitis and cystic fibrosis ... more ABSTRACT To understand the relationship between acute recurrent pancreatitis and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. An emerging number of patients present with a nonclassic phenotype of cystic fibrosis (CF) with partial features or single-organ disease only. The association between the phenotype of recurrent pancreatitis CFTR dysfunction is unclear. Patients with idiopathic recurrent pancreatitis were referred for electrophysiologic investigation. Thirty-three patients (18 males) aged 20+/-12 years with recurrent pancreatitis were studied. Three patients had mild asthma and 1 patient had mild ulcerative colitis. There was no family history of CF. All patients had normal imaging of the pancreatic duct by endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. No patient was pancreatic insufficient. Mean sweat chloride values were 41+/-14 meq/L (range: 18 to 64). Nasal potential difference (NPD) measurement was pathologic in 7 patients. Mean basal potential difference in these 7 patients was -33+/-13 mV and there was an abnormal response to chloride-free and isoproterenol solutions. There was no difference in sweat chloride concentration between the 2 groups. Mutation analysis revealed W1282X/5T, D1152H/5T, and W1282X/- in 3 patients with abnormal NPD and 1 W1282X allele was found in 1 patient with normal NPD. In this series, 21% of patients with recurrent pancreatitis have abnormalities of CFTR function. Patients presenting with recurrent, &quot;idiopathic&quot; pancreatitis require CFTR function testing.

Pediatric Crohn's Disease and Growth Retardation: The Role of Genotype, Phenotype, and Disease Severity

Pediatrics, Nov 1, 2004

Background. Delayed growth is a well-established feature of pediatric Crohn's disease. Severa... more Background. Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity.Methods. Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed.Results. NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively).Conclusions. Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure.

Neurological Manifestations of Celiac Disease in Children and Adults

Celiac disease (CD) is a common, life-long, autoimmune condition, affecting the small intestine o... more Celiac disease (CD) is a common, life-long, autoimmune condition, affecting the small intestine of genetically susceptible individuals. The classical clinical picture is disappearing as awareness progresses and the extra-intestinal presentation is emerging. Skin, endocrine, hepatic, skeletal, hematological, gynecological, infertility, dental, and behavioral abnormalities are emerging. Among the new growing domains is the extra-intestinal presentation of CD affecting the peripheral and central neurological systems. This review highlights neurological presentations in these patients, focusing on the clinical signs/symptoms in the pediatric and the adult age group, separately.

Is Enzyme Supplementation Effective Strategy to Reduce the Burden of Gluten Free Diet in Celiac Disease

International Journal of Celiac Disease, 2016

Several strategies have been considered for enzymatic detoxification of dietary gluten and to red... more Several strategies have been considered for enzymatic detoxification of dietary gluten and to reduce immunogenisity of gliadin peptides. An enzymatic therapy using enterically coated tablets containing caricain (Gluteguard), originated from a papaya, on celiac disease patients challenged with gluten was reported. Glut guard was able to protect these patients from adverse symptoms being induced by gluten challenge. The advantages of the fruit originated preparation are: it does not contain living microbes or bacterial purified or engineered products. It can be considered as a preventive therapy and further step in the future therapeutical strategy race for the celiac affected population benefits.

The Underdiagnosed Enemy: Africa Goes Celiac?

International Journal of Celiac Disease, 2019

Celiac disease incidence is continuously increasing worldwide and in Africa, where a clear North ... more Celiac disease incidence is continuously increasing worldwide and in Africa, where a clear North to South gradient is apparent. At least in the Maghreb region, the disease features resemble its European neighbors, but some aspects are completely different. The present review highlights the underdiagnosis and the inadequate nutritional therapy for celiac disease patients and summarizes the local special circumstances that should be address to coop with the contemporary load and future burden of the disease.

The Jigsaw Puzzle of Breast Feeding and Celiac Disease

International Journal of Celiac Disease, 2016

The puzzle of breast feeding effects on celiac disease development is complicated and despite num... more The puzzle of breast feeding effects on celiac disease development is complicated and despite numerous studies, remains unresolved. Several prospective or retrospective observational studies on the topic were reported, with contradictory results. The geoepidemiology teaches us that celiac disease incidence, in the west, is increasing, while breast feeding is decreasing, going along with the protective effect of mother’s milk. But, human milk and gluten are only two in the growing list of environmental factors that affect celiac disease induction or behavior. The recent increased knowledge on gluten side effects in non-celiac populations and the fact that human milk contains gluten peptides, further complicate the breast milk-gluten-celiac disease cross-talks. Latest studies revealed that breast feeding, whether exclusive or in combination with formula intake, did not reduce the risk of CD development. More so, recent publications concluded that timing of introduction of gluten to in...

The Gut-gut Axis: Cohabitation of Celiac, Crohn's Disease and IgA Deficiency

International Journal of Celiac Disease, 2016

An adult patient with IgA deficiency, celiac and Crohn’s disease is described. In addition to the... more An adult patient with IgA deficiency, celiac and Crohn’s disease is described. In addition to the rare association, he developed an unusual proximal Crohn’s disease. Unbalanced microbiome, increased intestinal permeability, susceptibility to infections that might initiate post translational modification of naive protein and the genetic background, are shared between the three entities. It is speculated that the IgA immune deficiency and its consequences are the early factors that set the stage for the progression of the other two diseases. Based on recent knowledge, special nutritional therapies should be considered, in addition to the gluten free diet.

Deamidated Gliadin Peptide Antibodies in Celiac Disease: A Diagnostic Driver or just along for the Ride?

International Journal of Celiac Disease, 2019

Anti deamidated gliadin peptides antibodies are considered as celiac disease associated diagnosti... more Anti deamidated gliadin peptides antibodies are considered as celiac disease associated diagnostic antibodies. They are in clinical use for almost the last two decades. In the first decade they were preferentially used in early childhood, in face of IgA deficiency and occasionally recommended as the prime serological marker, outperforming the anti-tissue transglutaminase autoantibody. Notably, they were recommended in combination with the tissue transglutaminase as enhancer of the diagnostic performances. No more, the circle turned over. In the second decade (2012-2019), most of the studies limited and criticized their past published advantages. They suggested that deamidated gliadin peptides antibodies do not have any advantage over anti-tissue transglutaminase autoantibodies in terms of early childhood, IgA deficiency, diagnostic performances and when both antibodies are combined. It seems that the deamidated gliadin peptide are losing their place in the celiac disease algorithmic...

[The Influence of Gluten on the Sharpness of Vision]

Harefuah, 2020

INTRODUCTION An eighty five old male was diagnosed with celiac disease. Six months before the dia... more INTRODUCTION An eighty five old male was diagnosed with celiac disease. Six months before the diagnosis he complained of difficulties in his sight. In an optimetrical examination a decline in sharpness of sight was found: Right (R) - 6/19, Left (L) - 6/12. Following a few months of a gluten-free diet his situation improved and the signs of celiac disease disappeared. The sharpness of sight was re-examined and good improvement was found: L - 6/9, R - 6/12. This means that gluten might influence the sharpness of sight.

Nonresponsive Celiac Disease Treated with a Unique Functional Medical Approach

International Journal of Celiac Disease, 2021

A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short statu... more A 16-year-old boy with nonresponsive celiac disease (NRCD), dermatitis herpetiformis, short stature, and failure to thrive, presented to this Functional Medicine practitioner because he had exceedingly high tissue transglutaminase (tTG) antibodies and poor growth, despite 10 months on a meticulous gluten-free diet (GFD). Immunological testing showed elevated antibody production against multiple peptides of wheat, food antigens, intestinal barrier dysfunction, lipopolysaccharide (LPS) antibodies, and polyreactive autoimmune reactions. An elimination diet, nutraceutical protocols to modulate the microbiome, address intestinal permeability, lower inflammation, and remove underlying bacterial infection were initiated. Global anti-inflammatory lifestyle modifications were recommended. Within 3 months of treatment, the patient's tTG antibodies decreased by 14% for the first time since strict gluten elimination. Within 15 months, tTG IgG antibodies were nearly normal at 1.61 (0.03-1.60, ELISA Index). Test results improved dramatically in tandem with clinical progress. On a GFD and after initiating and maintaining these dietary and lifestyle changes, he gained 12 inches and 40 pounds. To our knowledge, this is the first published case of complete reversal of NRCD and failure to thrive by addressing endotoxin and lifestyle outside of a GFD.

Candida albicans in celiac disease: A wolf in sheep’s clothing

Autoimmunity Reviews, 2020

The purpose of this study was to evaluate the cytotoxic effects of commercially available root ca... more The purpose of this study was to evaluate the cytotoxic effects of commercially available root canal sealers [Sealite Ultra (SU), Tubli-Seal (TS), Tubli-Seal EWT (TS-EWT), Pulp Canal Sealer (PCS), Pulp Canal Sealer EWT (PCS-EWT), Endomethasone N (En N), and Apexit Plus (AP)] on L929 cells by using MTT assay. After incubation with each sealer's extract at 37°C in a humidified air atmosphere containing 5% CO 2 for 24 h, MTT (5 mg/mL) in saline was added into each well and further incubated at 37°C for 4 h. Formazan precipitate was dissolved in a buffer containing 23% sodium dodecyl sulfate and 50% N,N-dimethylformamide (pH 4.7). Optical densities of dissolved formazan were read using a microplate spectrophotometer. AP, TS, and TS-EWT showed no cytotoxicity at any dilution tested. Other sealers exhibited some degree of cytotoxicity at the 1/4 and 1/2 dilutions. PCS-EWT and SU exerted more potent cytotoxicity at 1/2 dilution than the other sealers.

Food Industrial Microbial Transglutaminase in Celiac Disease: Treat or Trick

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, Mar 31, 2015

The surge in incidence of celiac disease (CD) is due more to environmental than to genetic change... more The surge in incidence of celiac disease (CD) is due more to environmental than to genetic changes. It is paralleled by a food industry that is continuously introducing additives to processed products. Microbial transglutaminase (mTG) is an enzyme that deamidates/transamidates proteins, enabling cross-linkage of molecules and revolutionizing the properties of many food products. It belongs to the family of transaminases and tissue transglutaminase (tTG) has been identified as the autoantigen in CD. Both enzymes de/transamidate gluten, the nutritional environmental factor that induces CD. Although several studies have shown that mTG transamidation of wheat flour/gluten can detoxify gluten peptide in vitro, by inhibiting the response to intestinal gliadin, inducing T cells and reducing INFγ production without influencing their main technological properties, a word of caution is advised. The oral challenge of adult CD patients with mTG transamidated flour was found to be only partially effective, not fulfilling expectations, and there have been multiple recent observations that indicate that mTG transamidated flour/gluten could be dangerous to gluten sensitive populations: mTG cross-linking of gluten may be hazardous in CD since the enzyme can deamidate gluten, thus mimicking endogenous tTG, it can link an extensive repertoire of proteins and other macromolecules with immunogenic potential, mTG treated gluten peptides are immunogenic to celiac patients, inducing specific IgA antibodiesand are recognized by gluten-specific humanT cells. Their effect on CD intestinal permeability has not yet been studied. To better understand the actual processes and events, associated with the suggested mTG therapy, long-term ex vivo and in vitro studies are needed. Until then, it is best to respect the data but suspect the safety of the gluten sensitive populations.

Celiac Disease: Intestinal, Heart and Skin Interconnections

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, Mar 31, 2015

The first description of celiac disease associated with dilated cardiomyopathy and pellagra in th... more The first description of celiac disease associated with dilated cardiomyopathy and pellagra in the same person, brings multiple interesting aspects to discuss. Celiac disease is prevalent in cardiac failure and vice versa, multiple cardiac manifestations exist in celiac disease. Pathophysiologically, autoimmune, nutritional, infectious and thrombophilic pathways can be involved. In some cases the cardiomyopathy respond to gluten free diet. Multiple cutaneous manifestations, including pellagra like rash, were described in CD. Autoimmune mechanisms and much more, (e.g. nutrient deficiencies) might aggravate the skin manifestation. The present editorial highlights the cardiac-cutaneous-intestinal cross talks in celiac disease in order to increase the awareness of the physician community to speed up celiac disease diagnosis in those extraintestinal manifestations.

Transient Anti TG2 Autoantibodies in Systemic Lupus Erythematosus: A Window to Autoimmunity

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease

Transient anti transglutaminase2 and anti endomysial antibody elevation in systemic lupus erythem... more Transient anti transglutaminase2 and anti endomysial antibody elevation in systemic lupus erythematosus is fundamentally thought-provoking with respect to establishment of autoimmunity and its progression. Celiac disease and systemic lupus erythematosus are both relayed within the mosaic framework of autoimmunity. Transglutaminase2 is a multifunctional enzyme, involved in cell biology and survival and is one of the post translational modifiers of protein, enhancing autoimmunity. TG2 and its specific antibodies are heavily involved in celiac disease. TG2 is essential in clearance of apoptotic cells and experimentally participates in systemic lupus-like induction. However, the role of anti TG2 autoantibodies is far from being unraveled. Despite disappearance of these antibodies on gluten containing diet, in the present case, the boy is at risk of developing celiac disease in the future.

Serological Markers and/or Intestinal Biopsies in the Case-finding of Celiac Disease

by International Journal of Celiac Disease, Matthias Torsten, and aaron lerner

International Journal of Celiac Disease

The new 2012 ESPGHAN guidelines for the pediatric diagnosis of celiac disease (CD) unraveled and ... more The new 2012 ESPGHAN guidelines for the pediatric diagnosis of celiac disease (CD) unraveled and stimulated an old/new discussion on the most efficient case- finding in pediatric CD. The fine balance between reliable serological markers and the gold diagnostic standard of small bowel histology is somewhat better understood. Due to a low diagnostic rate, changes in phenotype, increased incidence, epidemiological shifts, importance of early implementation of gluten free diet to prevent complications, the case-finding of CD should be improved. Our adult gastrointestinal colleagues did not adopt ESPGHAN diagnostic criteria and within the pediatric gastroenterology community, controversies exist. The present editorial on pediatric CD complements an adult CD one. It expands on the drawbacks, limitations and criticisms of the guidelines and calls for prudency, further research and follow-up studies. Until recent observations are implemented in the future guidelines, small bowel histology should remain the gold standard for case-finding in CD.

Increased Knowledge and Awareness of Celiac Disease will Benefit the Elderly

by aaron lerner and International Journal of Celiac Disease

International Journal of Celiac Disease, Sep 12, 2015

Celiac disease, once deemed to be primarily a pediatric disease, is accepted nowadays as a lifelo... more Celiac disease, once deemed to be primarily a pediatric disease, is accepted nowadays as a lifelong disease that increasingly affects the elderly. In older patients it is late and underdiagnosed, it is hypo- or asymptomatic and case finding strategy is recommended. Gluten restrictive therapy is problematic but manageable and beneficial, improving symptoms, serology, histology and preventing complications. Increased knowledge and awareness on CD in the third age and a comprehensive, multidisciplinary and holistic approach will improve their outcome.

Outside of Normal Limits: False Positive/Negative Anti TG2 Autoantibodies

by aaron lerner and International Journal of Celiac Disease

International Journal of Celiac Disease, Sep 12, 2015

Detection of IgA-transglutaminase2 (TG2) autoantibodies has become the test of choice for the dia... more Detection of IgA-transglutaminase2 (TG2) autoantibodies has become the test of choice for the diagnosis and monitoring of celiac disease (CD), and is recommended as the serological ‘gold standard’ by most of the CD societies. Despite its wide acceptance and reasonable performance, several aspects are problematic and disputed. The normal range levels between positivity and negativity are modified, manufacturers’ cut-off levels are extremely variable, far from matching in house determinations, insufficient standardization, inadequate reference protocols and no reliable quality assessment of the ELISA antibody (AB) kits for CD diagnosis and follow-up of dietary adherence. Numerous limitations exist in its detection, diagnosis, and follow-up capacities, resulting in frequent clinical circumstances when professionals encounter false positive and negative situations. The present review updates and discusses these facets and aims to extend our knowledge and help CD associated professionals to use the IgA-TG2 antibodies appropriately. We hope that the content of the review will stimulate the scientific community to explore and better delineate the role and functions of the AB and the industrial manufacturers to improve clinical performance of their diagnostic tests.

The World Incidence and Prevalence of Autoimmune Diseases is Increasing

by International Journal of Celiac Disease and aaron lerner

Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westerniz... more Epidemiological data provide evidence of a steady rise in autoimmune disease throughout Westernized societies over the last decades. Multiple publications exist, describing past or actual incidences/prevalence of individual autoimmune diseases, however, long term studies on selected populations are scarce. Aims: to calculate the % increases per year of autoimmune diseases frequencies worldwide, analyze the differential increases per country and disease, and identify geoepidemiological trends. Methods: A systematic review was performed to identify incidence and prevalence of autoimmune diseases. 30 Studies from the last 30 years were identified using Medline, Google, and Cochrane Library databases. Only long-term regional or national follow-ups are reported. Results: The means ± s.d. of the net % increased /year incidence and prevalence of autoimmune diseases worldwide were 19.1±43.1 and 12.5±7.9, respectively. Rheumatic, endocrinological, gastrointestinal and neurological autoimmune diseases revealed the following annual % increases per year: 7.1, 6.3, 6.2, and 3.7, respectively. In all of these, differences between old vs new frequencies were highly significant (p< 0.0001). Comparing various autoimmune diseases, celiac disease increased the most and the highest increase in incidence, comparing old to new surveys is allocated to myasthenia gravis. Despite considerable variations between the countries, celiac, type 1 diabetes and myasthenia gravis frequencies increased the most in Canada, Israel and Denmark, respectively. Frequencies of the autoimmune diseases increased significantly in the West and North when compared to East and South, respectively. Conclusions: Despite multiple reports on autoimmune diseases frequencies, long-term longitudinal follow-ups are scarce. Incidences and prevalences have increased significantly over the last 30 years. Rheumatic, endocrinological and gastrointestinal autoimmune diseases in Israel, Netherlands, USA and Sweden increased the most. These observations point to a stronger influence of environmental factors as opposed to genetic factors on autoimmune disease development.

Gut-bone Cross Talks and Implications in Celiac Disease

by International Journal of Celiac Disease and aaron lerner

Metabolic bone disease is a frequent extra-intestinal co-morbidity in newly diagnosed, mostly adu... more Metabolic bone disease is a frequent extra-intestinal co-morbidity in newly diagnosed, mostly adult patients who have 70% low bone mineral density. Musculoskeletal signs and symptoms, osteopenia, osteoporosis and fractures are the most frequent manifestations. The etiology is multifactorial, however, micronutrient malabsorption, mainly of calcium and vitamin D, secondary hyperparathyroidism and inflammation are the main driving forces. The diagnosis is based on signs and symptoms, biochemical and endocrinologic laboratory evaluation and imaging by dual x-ray absorptiometry. Treatment of low bone mineral density in CD comprises: a gluten free diet, coverage of nutritional deficiencies (including calcium and vitamin D), changes in life style and if necessary, pharmacologic and hormonal replacement therapy. The cost effectiveness of those therapy methods were barely assessed. Understanding the pathophysiology of bone loss in celiac disease might bring new therapeutical strategies for the patient's benefit.

Intraepithelial Lymphocyte Normal Cut-off Level in Celiac Disease: The Debate Continues

by International Journal of Celiac Disease and aaron lerner

The gold standard for diagnosis of celiac disease is positive serology confirmed by histological ... more The gold standard for diagnosis of celiac disease is positive serology confirmed by histological evidence of small intestinal biopsy damage as determined by the modified Marsh classification. Intraepithelial lymphocyte count has a pivotal importance in this grading criteria and the normal cutoff density has paramount importance in distinguishing between celiac disease and normal or false+ conditions. However its determination is problematic, complicated and far from being standardized. The localization along the villi or along the small bowel, the section thickness, the mode of detection and analysis, geoepidemiological influences, age dependency, associated infections or diseases and the strictness of the inclusions/exclusion criteria of the normal control group, all affect IEL density and normal cutoff levels. It is hoped that after standardization, the cutoff levels of IELs will better reflect the in-vivo reality to distinguish celiac disease from normal and associated conditions that affect intestinal IEL count.

The Gut-gut Axis: Cohabitation of Celiac, Crohn's Disease and IgA Deficiency

by aaron lerner and International Journal of Celiac Disease

An adult patient with IgA deficiency, celiac and Crohn's disease is described. In addition to the... more An adult patient with IgA deficiency, celiac and Crohn's disease is described. In addition to the rare association, he developed an unusual proximal Crohn's disease. Unbalanced microbiome, increased intestinal permeability, susceptibility to infections that might initiate post translational modification of naïve protein and the genetic background, are shared between the three entities. It is speculated that the IgA immune deficiency and its consequences are the early factors that set the stage for the progression of the other two diseases. Based on recent knowledge, special nutritional therapies should be considered, in addition to the gluten free diet.

Is Enzyme Supplementation Effective Strategy to Reduce the Burden of Gluten Free Diet in Celiac Disease

by International Journal of Celiac Disease and aaron lerner

Several strategies have been considered for enzymatic detoxification of dietary gluten and to red... more Several strategies have been considered for enzymatic detoxification of dietary gluten and to reduce immunogenisity of gliadin peptides. An enzymatic therapy using enterically coated tablets containing caricain (Gluteguard), originated from a papaya, on celiac disease patients challenged with gluten was reported. Glut guard was able to protect these patients from adverse symptoms being induced by gluten challenge. The advantages of the fruit originated preparation are: it does not contain living microbes or bacterial purified or engineered products. It can be considered as a preventive therapy and further step in the future therapeutical strategy race for the celiac affected population benefits.

Nutrients, Bugs and Us: The Short-chain Fatty Acids Story in Celiac Disease

by International Journal of Celiac Disease and aaron lerner

The gut ecosystem with myriads of microorganisms and the high concentration of immune system cell... more The gut ecosystem with myriads of microorganisms and the high concentration of immune system cells can be considered as a separate organ on its own. The balanced interaction between the host and microbial cells has been shaped during the long co-evolutionary process. In dysbiotic conditions, however, this balance is compromised and results in abnormal interaction between the host and microbiota. Celiac disease is such an example were dysbiotic and metabolic signature are shaping the disease progression in genetically susceptible individuals. Short chain fatty acids are bacterial originated metabolic messenger between the pathobionts and the intestinal mucosa. Their local luminal effects and systemic ones were just recently unraveled. Accumulating data attribute multiple beneficial effects to them. Changes in microbiota and their short-chain fatty acids production is clearly related to the pathogenesis of celiac disease and might open new therapeutic strategies to combat the disease.

The Jigsaw Puzzle of Breast Feeding and Celiac Disease

by International Journal of Celiac Disease and aaron lerner

The puzzle of breast feeding effects on celiac disease development is complicated and despite num... more The puzzle of breast feeding effects on celiac disease development is complicated and despite numerous studies, remains unresolved. Several prospective or retrospective observational studies on the topic were reported, with contradictory results. The geoepidemiology teaches us that celiac disease incidence, in the west, is increasing, while breast feeding is decreasing, going along with the protective effect of mother's milk. But, human milk and gluten are only two in the growing list of environmental factors that affect celiac disease induction or behavior. The recent increased knowledge on gluten side effects in non-celiac populations and the fact that human milk contains gluten peptides, further complicate the breast milk-gluten-celiac disease cross-talks. Latest studies revealed that breast feeding, whether exclusive or in combination with formula intake, did not reduce the risk of CD development. More so, recent publications concluded that timing of introduction of gluten to infant diet did not influenced the risk of development of CD. It is hypothesized that local environments, nutritional habits, intestinal ecosystems or genetic background might have influenced the published results. Much more epidemiological and prospective investigational studies might clarify the jigsaw puzzle of breast feeding and celiac disease behavior.

The Gut-stomach Axis: Helicobacter pylori and Celiac Disease

by International Journal of Celiac Disease and aaron lerner

Abnormalities in the gastric and duodenal ecosystems have been proposed as contributing to the pa... more Abnormalities in the gastric and duodenal ecosystems have been proposed as contributing to the pathophysiology of celiac disease (CD) and Helicobacter pylori (Hp) infection, respectively. Lymphocytic gastritis and lymphocytic duodenitis cohabit in Hp and celiac disease and also in Hp-or non-CD respective conditions. The present editorial discusses those entities, concentrating on the pathophysiological pathways, highlighting the Hp-CD relationship in the contest of the gut-stomach axis.

Beyond the Joint: What's Happening in the Gut

by International Journal of Celiac Disease and aaron lerner

Rheumatoid arthritis and celiac disease belong to the autoimmune disease family. Despite being se... more Rheumatoid arthritis and celiac disease belong to the autoimmune disease family. Despite being separate entities they share multiple serological and genetic aspects. Celiac disease associated serum bio-markers are observed in rheumatoid arthritis. Contrary to their specific HLA predisposition , the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to celiac disease and rheumatoid arthritis susceptibility, connecting bugs and us and autoimmunity. The present editorial updates and clarifies those aspects.

Autoimmune Thyroid Diseases in Celiac Disease: If and When to Screen

by International Journal of Celiac Disease and aaron lerner

Prevalence of autoimmune thyroiditis is increased in patients with celiac disease and vice versa.... more Prevalence of autoimmune thyroiditis is increased in patients with celiac disease and vice versa. Both diseases are frequent autoimmune diseases sharing multiple aspects lodging at the two ends of the gut-thyroid axis where the cross-talks' pathways are still unrivalled. Many authors recommend screening patients with thyroid autoimmunity for celiac disease associated antibodies. However, routine screening of celiac patients for anti-thyroid antibodies is less clear. Despite the fact that the latter screening fulfills most of the criteria for screening a disease, the timing and cost-effectiveness remains undetermined. For now, in face of celiac disease, the increased prevalence of autoimmune thyroid diseases needs to be taken in account and the accurate diagnosis should not be delayed.

Extra Intestinal Manifestations of CD: Common Pathways in the Gut-remote Organs' Axes

by International Journal of Celiac Disease and aaron lerner

Genetic and environmental risk factors for celiac disease are well established, however, the prec... more Genetic and environmental risk factors for celiac disease are well established, however, the precipitating events leading to development of celiac disease and associated conditions remain enigmatic. Being a multi-faced, multi-organ disease and the multiple extra intestinal phenotypes of celiac disease, further more add to its complexity. The present editorial summarizes the potential mechanisms connecting gut eco system events to remote organ manifestations and dysfunctions in celiac disease. It is suggested that nutrients, the microbiome/dysbiome interplay, the local post translational modification of naive proteins, the leaky gut and the leaked immunogenic or toxic molecules or complexes and the circulating pro-inflammatory immune cells and cytokines are at the basis of the gut-remote organ pathologies, in CD.

Can Celiac Disease Present Along With Childhood Obesity

by International Journal of Celiac Disease and aaron lerner

Celiac disease is an autoimmune, gluten-induced enteropathy with a prevalence of 1-1.5% in Wester... more Celiac disease is an autoimmune, gluten-induced enteropathy with a prevalence of 1-1.5% in Western populations. It may present with classical gastrointestinal symptoms, non-gastrointestinal symptoms or as an asymptomatic disease. Cases of childhood obesity in gluten sensitive enteropathy have been recently reported. The study aimed to retrospectively evaluate the rate of overweight and obesity prevalence in a large sample of celiac children in comparison to non-celiac group, and to investigate the weight dynamics following gluten-free diet. Among 390 patients, 68 (17.4%) (29 boys) were overweight or obese at diagnosis. Gluten-free diet did not shown a beneficial effect on weight. The study demonstrates comparable rates of overweight and obesity in celiac versus non-celiac population.

Polyautoimmunity - The missing ingredient

by Samasca Gabriel, Sur Daniel, Aldea Cornel, Sur Lucia, and aaron lerner

Autoimmunity Reviews, 2018

no abstract

Challenges in Gluten-free diet in celiac disease: Prague consensus

by Iulia Lupan, Samasca Gabriel, and aaron lerner

New treatments in celiac disease are being vigorously pursued to either replace or facilitate the... more New treatments in celiac disease are being vigorously pursued to either replace or facilitate the difficult-to-follow gluten-free diet. There are numerous difficulties in adhering to gluten withdrawal, but the adolescence and young adulthood is considered a fragile and high risk period for intentional and unintentional gluten intake. This is only one of the aspects that were reviewed and recommendations issued, in the Prague consensus report on the transition from childhood to adulthood in celiac disease patients. The present review intends to summarize the challenges in gluten-free diet adherence during the transitional period, as reflected in the last Prague concensus, published in 2016. The honorable panel members recommended that dietary adherence and the consequences of non-adherence represent key components for discussion in the transitional period setting.

Gluten-free Diet -Tough Alley in Torrid Time

by International Journal of Celiac Disease and aaron lerner

Dietitians play a pivotal role in the education, follow-up and navigation of the gluten-free diet... more Dietitians play a pivotal role in the education, follow-up and navigation of the gluten-free diet for patients affected by celiac disease. Since gluten withdrawal is the cornerstone of celiac disease therapy, and since various future therapeutic strategies, are not yet on the market, the patients relay heavily on the registered dietitian nutritionists (RDNs) advice and service to cope with the gluten-free diet tough alley. Unfortunately, gluten withdrawal, nowadays, represent also a torrid time. The actual surge in incidence, wheat content, gluten intake, celiac disease-related T-cell stimulatory epitopes in wheat, usage in the processed food industries, nutritional deficiencies, changing phenotype and the fact that gluten is potentially detrimental to humankind health, make the RDNs role more complex, difficult and challenging. The present review expands on the gluten-free diet related tough alley in torrid time, which the registered dietitian nutritionists are facing when dealing with gluten-sensitive patients.

Anti-tTg-IgA is neither a Solved Problem nor a " closed case " in Celiac Disease Diagnosis

by International Journal of Celiac Disease and aaron lerner

Anti-tissue transglutaminase (tTg) IgA are considered the most frequently used serological marker... more Anti-tissue transglutaminase (tTg) IgA are considered the most frequently used serological marker for celiac disease diagnosis. Despite its recommended leading position by the 2012 ESPGHAN diagnostic criteria, it exposes multiple false positive and negative titers. In view of the critical opinions expressed lately in the literature against the application of those criteria, the bias in the central place occupied by tTg-IgA in the new ESPGHAN CD Diagnostic Guidelines and the emergence of newer serological marker for celiac disease, it is hoped that the revised guidelines will open up the limited, problematic and single Tg2-IgA antibody for other or additional single or combined serological diagnostic markers.

A Silent or Hypo-symptomatic Disease Can Erupt: Acute Presentations of Celiac Disease

by International Journal of Celiac Disease and aaron lerner

Celiac disease is a multi-organ disorder which is highly variable in its clinical expression, pre... more Celiac disease is a multi-organ disorder which is highly variable in its clinical expression, presenting multiple enteric and extraintestinal manifestations. However, most of treating physicians and dieticians regard celiac disease as a chronic, gradually evolving, asymptomatic or hypo-symptomatic entity. The present mini-review aims to screen the literature for acute presentations of celiac disease and to increase the awareness of the medical communities, for such a possibility. It appears that the disease can present acutely in multiple symptomatic, phenotypic and laboratory pictures. The acute presentation involves mainly the gastrointestinal tract and adjacentorgans like liver and gallbladder, however, extraintestinal and remote organs presentations can occur.

International Journal of Celiac Disease: Four Year Interval Summary

by International Journal of Celiac Disease, aaron lerner, and Matthias Torsten

International Journal of Celiac Disease (IJCD) is an international clinical and scientific journa... more International Journal of Celiac Disease (IJCD) is an international clinical and scientific journal that aims to cover the multiple aspects of celiac disease (CD). With the renewal of the new year of 2018, the IJCD is celebrating four years of academical publications of 170 articles. The objective recognition by the medical, paramedical and the scientific community, represented by the substantial number of articles' views, downloads, likes and citations, is indicative of a proliferative and successful journal, at least for its first four years.

Celiac Disease and Lactose Intolerance

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, 2018

Celiac disease and lactose intolerance are nutritional diseases where withdrawal of a specific nu... more Celiac disease and lactose intolerance are nutritional diseases where withdrawal of a specific nutrient is therapeutical. Celiac disease is underdiagnosed while lactose intolerance is over diagnosed, including in naïve or treated celiac patients. The present review highlights myths and realities and revisits common misconceptions in the relationship between celiac disease and lactose intolerance. It is hoped that the care providers will increase the rate of diagnosis of celiac disease, while decreasing the over diagnosis of lactose intolerance for the benefit of the patients.

The Gut Feeling of the Joints: Celiac Disease and Rheumatoid Arthritis Are Related

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, 2019

The "mosaic of autoimmunity" is a complex, multiple-faceted, challenging scientific enigma. Celia... more The "mosaic of autoimmunity" is a complex, multiple-faceted, challenging scientific enigma. Celiac disease and rheumatoid arthritis are part of the autoimmune bee hive and despite being separate entities, they share multiple aspects. The present review summarizes the epidemiological, clinical, serological, genetic, environmental, enteric eco-events and associated diseases shared by the two mechanistically similar though different antigenic entities.

Milk Proteins as a Trigger for Autoimmune Diseases: Myth or Reality

by International Journal of Celiac Disease and aaron lerner

10.12691/ijcd-8-1-2, 2020

Humans started to drinkmammal's milk 11,000 years ago. Nowadays, cow, goat and sheep milks accoun... more Humans started to drinkmammal's milk 11,000 years ago. Nowadays, cow, goat and sheep milks account for about 87% of the world milk production. The high incidence of allergies to cow's milk components and autoimmune diseases is rising in the Western industrialized countries, where milk is a major dietary component, especially in processed foods. When allergenic milk proteins face immature and susceptible immune system in children it might represent a threat for future health. Several studies support strong evidences that exposure to dietary allergens during childhood can increase the risk of developing autoimmune diseases, such as type 1 diabetes, celiac disease, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, neuropsychiatric disorders, among others. The "Mosaic of Autoimmunity" elucidates the diversity and multifactorial origin of autoimmune disease expression in humans. Growing evidence suggests a large overlap between oral tolerance, food antigens and autoimmune diseases. Assorted mechanisms have been hypothesized to explain the connection between these entities, mainly involving molecular mimicry, shared epitopes, cross-reactivity phenomena, enhanced hosts gut permeability, change in microbiome/ dysbiome ratio and even involving Mycobacterium avium subspecies paratuberculosis infection. Nowadays, different kinds of milk and dairy products are being evaluated for a potential benefit in human health. Likewise, milk derived nutraceutical products, such as bovine colostrum, claim many clinical advantages especially for its immune modulatory capabilities. The aim of this review is to explore the impact of cow's milk protein son human health, emphasizing its relationship with immune mediated and autoimmune diseases.

Covid-19 and the Human Gut: A New Runner on the Tract

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, 2020

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) dwells in the respiratory airway... more The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) dwells in the respiratory airways, however, its digestive tract presence, infectivity, mucosal attachment and penetrating mechanisms, enteric proliferation, stool shading, flashed bio-aerosol spreading and fecal-oral transmission is far from being understood. The present review opens some skylights to lighten the long, tortuous, dark and challenging tunnel of the gastrointestinal tract and his uninvited covid-19 viral new inhabitant.

Sjögren’s Syndrome Associated with Celiac Disease

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, 2020

Background: Autoimmune diseases tend to run in families and the affected persons are prone to add... more Background: Autoimmune diseases tend to run in families and the affected persons are prone to additional autoimmune conditions. This is the case for celiac disease (CD) and Sjögren's syndrome (SS). Objectives: To describe a patient with both diseases and to analyze the clinical, therapeutic and evolutionary characteristics of published patients with SS associated with CD. Methodology: A systematic review of articles published in PubMed, MEDLINE, LILACS and Scielo dating from 1966 to May 2020, was conducted, using the following search words: Sjögren's syndrome, Celiac disease. Only English, German and French publications were considered. Results: Only 16 studies with 31 patients with SS associated CD were depicted. Adding the present case would mount the total to 17 studies, describing 32 patients. There are 6 observational studies and 10 case reports. In relation to demographics, age varied from 10 to 73 years old, with a median of 45 years and the great majority were female (21/32 patients). SS preceded CD manifestations in 7 studies, CD was the first presentation in 6 articles and simultaneous diseases was observed in 4 reports. Time elapsed between the two diseases varied from 2 to 33 years. Autoantibodies related to SS showed that anti-Ro and anti-La were positive in 8/17, while CD-related antibodies were positive in 12/17 studies. Regarding therapy, the majority received a gluten-free diet as CD therapy (13/17 studies). Glucocorticoid was prescribed in 6/17 studies and hydroxychloroquine in 4/17. When described, all studies demonstrated improvement of CD manifestations and 7/17 improved SS symptoms. Conclusion: The present comprehensive review evaluated all published cases of SS and CD of the literature. In the majority, SS precedes CD and all patients had good responses to appropriate therapy. It is hoped that increased awareness of the combination of SS and CD will result in earlier diagnosis and therapy and improved outcome.

The Gut Feeling of the Heart: Pathophysiological Pathways in the Gut-heart Axis in Celiac Disease

by International Journal of Celiac Disease and aaron lerner

International Journal of Celiac Disease, 2020

The chain of events, starting from nutrients that change microbiome/dysbiome ratio followed by th... more The chain of events, starting from nutrients that change microbiome/dysbiome ratio followed by their secreted mobilome and ending with the leaky gut syndrome, can be applied for cardiovascular diseases. The Gut-heart axis is only one avenue where intestinal luminal eco-events induce remote organ's pathology. The present editorial highlights the mechanisms and potential pathways in the nutrients-microbiota-endocrine-cardiovascular axis that might affect human heart morbidity and mortality in celiac disease.