Journal of Gastrointestinal and Liver Diseases, 2014
Background & Aim. Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune ... more Background & Aim. Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients.Methods. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy.Results. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phospha...
Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that ca... more Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.
Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C ... more Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10. 1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected = .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.
Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test,... more Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.
Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Co... more Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Coeliac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. In recent years, the Internet and the non-medical press have reported a correlation between gluten-related disorders and fibromyalgia-like symptoms. The aim of our study was to verify a possible association between FM and CD, by assessing the prevalence of CD in a cohort of FM patients and vice versa. 90 consecutive subjects from our Rheumatologic outpatient clinic who had been diagnosed with FM were serologically tested for CD and positive patients underwent esophagogastroduodenoscopy to obtain duodenal biopsies. A second group of 114 consecutive subjects from our Coeliac Disease outpatient clinic were investigated for the presence of FM-like symptoms through a questionnaire. Patients reporting chronic widespread pain were addressed to a rheumatologist for ...
Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, ... more Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.
We have studied the frequency of HLA-DR,-MT, and-MB antigens in adult patients with coeliac disea... more We have studied the frequency of HLA-DR,-MT, and-MB antigens in adult patients with coeliac disease and in a group of healthy controls, evaluating the strength of the observed associations by measuring the aetiologic fractions. Among the antigens significantly associated with coeliac disease, MB2 (DQw2) showed an aetiologic fraction higher than those of DR3 and DR7. Our results suggest that MB2, as associated more frequently than other specificities with a hypothetical disease predisposing gene, may play a role in the pathogenesis of coeliac disease. The significant association of DR3 and DR7 with coeliac disease may be ascribed to linkage disequilibrium of these antigens with MB2. A number of immunologic diseases have been reported in association with HLA-DR antigens which are retarded as human homologues of murine Ta antigens. Recently increasing evidence has suggested that two additional series of Ta genes code for two additional series of Ia antigens termed MB2 and MT.3 Little is known about the association of these newly defined antigens and disease, but MB1 and MT2 have been reported associated with systemic lupus erythematosus4 and primary sicca syndrome.5 Moreover, it is noteworthy that the association between MB1 and systemic lupus erythematosus4 and between MT2 and primary sicca syndrome5 has been shown to be stronger than those between DR antigens and the above mentioned conditions. These clinical studies suggest that MB and MT antigens may be more important than DR in genetic predisposition to some diseases. In view of this we have studied the frequency of MB and MT antigens in coeliac disease, a condition known to be associated with DR alleles DR3 and DR7.6 Methods PATIENTS Fifty one biopsy proven coeliac patients (aged 15-68 years, mean 38-7 years) were typed for DR and MT antigens. The control group was made up of 56
We measured splenic function using a simple, non-isotopic method in childhood coeliac disease. No... more We measured splenic function using a simple, non-isotopic method in childhood coeliac disease. No patients were shown to have hyposplenism. This has important clinical and therapeutic implications.
EDITOR vs 5). Among reflux patients, the PT4 was always higher in the supine position than in the... more EDITOR vs 5). Among reflux patients, the PT4 was always higher in the supine position than in the upright position (44 vs 10% for nAR and 34 vs 10% for AR patients). This difference was significant (P < 0.05). Peptide Levels. No significant difference was evident for peptide between the four (nAnR, nAR, AnR and AR) groups of patients studied (Table 1). Peptide Integrated Response to Test Meal. As was the case for the basal hormone levels, the integrated response to the test meal did not differ between the four groups of patients (Table 1) regardless of the peptide being considered. These results suggest strongly that alterations in basal or food-stimulated plasma levels of motilin, cholecystokinin, somatostatin, gastrin, or neurotensin are not causally related with asthma in patients with gastroesophageal reflux.
Ninety patients whose spleen had been removed either because of trauma (41 cases) or as an electi... more Ninety patients whose spleen had been removed either because of trauma (41 cases) or as an elective procedure (49) were investigated for return of splenic function by counting pitted red cells and examining spleen scans made after injection of heat damaged 99mTc labelled red cells. There was no significant difference in the proportion of pitted red cells between the two groups of patients. Evidence of splenic tissue in scintiscans was not invariably associated with low pitted 'red cell values, suggesting that the presence of splenic tissue did not necessarily mean return of splenic function. In every patient whose proportion of pitted red cells was less than 16.2% the scintiscan showed splenic uptake. The proportion of patients with pitted red cell values below 16 2% was significantly higher in the group operated on for trauma, and it is concluded that this was due to splenosis. A high inverse correlation between pitted red cell counts and computed splenic volumes was found. Patients with pitted red cell values of less than 16 2% had computed volumes of 22-133 cm3; below this range the proportion of pitted red cells rose very sharply. These results confirm that splenosis occurs in adults, though less often than in children, and suggest that when splenic tissue is to be implanted a graft of at least 20-30 cm3 is needed to ensure satisfactory return of splenic function.
erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, whi... more erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, which may be accompanied by acute phase reactants. The relationship between EHOA and classical osteoarthritis (OA) is still controversial, since some authors consider EHOA as a distinct disease, other as a subset of OA, and some as a border entity between OA and rheumatoid arthritis (RA). Scarce data are available about the seroimmunological profile of the disease, which could aid to identify a possible role of the immune system in EHOA pathogenesis, and could also allow to better differentiate EHOA both from OA and RA. blood was drawn from the following patients: 37 with EHOA, 35 with OA and 45 with RA. All sera were tested for rheumatoid factor, anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), anti-extractable nuclear antigens (anti-ENA) and anti-neutrophil cytoplasmic antibodies (ANCA). ANCA were never detected in OA, whereas they were found in 7 (19...
Journal of Gastrointestinal and Liver Diseases, 2014
Background & Aim. Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune ... more Background & Aim. Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients.Methods. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy.Results. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phospha...
Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that ca... more Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.
Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C ... more Our aim was to investigate whether host genetic factors are involved in the onset of hepatitis C virus (HCV)-related mixed cryoglobulinemia (MC). We studied 25 consecutive patients presenting with a full-blown clinical picture of MC by physical examination, blood chemistry, assessment of cryoglobulins and their composition, nonorgan-specific autoantibodies, antibodies to HCV, serum HCV RNA, and HLA polymorphism. Biopsies of liver, bone marrow, and minor salivary glands were also performed in a number of patients. HLA results were compared with those of normal controls and patients with chronic HCV infection without MC and negative for autoimmune phenomena (pathological controls). Type II MC was found in 14 of 25 patients (56%), and type III MC was found in the remaining 11 (44%). All patients were positive for antibodies to HCV and/or serum HCV RNA. HLA-B8 was found in 40% (10 of 25) of patients compared with 10. 1% (38 of 377) of normal controls (P = .00003, Pcorrected = .0005, relative risk [RR] 5.9) and 6.7% (2 of 30) of pathological controls (P = .007, Pcorrected = not significant). As for class II HLA molecules, only DR3 was significantly more frequent in MC patients (40%, 10 of 25) than in normal controls (15.1%, 57 of 377; P = .003, Pcorrected = .03, RR 3.7). Odds ratio (OR) for the risk of developing MC was calculated in patients positive for B8 and/or DR3, and the highest OR (8.2) was observed in individuals possessing both. The results suggest that the development of HCV-related MC is associated with HLA-B8 and DR3 markers.
Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test,... more Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first-degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease.
Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Co... more Fibromyalgia (FM) association with autoimmune diseases has been widely reported in literature. Coeliac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. In recent years, the Internet and the non-medical press have reported a correlation between gluten-related disorders and fibromyalgia-like symptoms. The aim of our study was to verify a possible association between FM and CD, by assessing the prevalence of CD in a cohort of FM patients and vice versa. 90 consecutive subjects from our Rheumatologic outpatient clinic who had been diagnosed with FM were serologically tested for CD and positive patients underwent esophagogastroduodenoscopy to obtain duodenal biopsies. A second group of 114 consecutive subjects from our Coeliac Disease outpatient clinic were investigated for the presence of FM-like symptoms through a questionnaire. Patients reporting chronic widespread pain were addressed to a rheumatologist for ...
Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, ... more Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.
We have studied the frequency of HLA-DR,-MT, and-MB antigens in adult patients with coeliac disea... more We have studied the frequency of HLA-DR,-MT, and-MB antigens in adult patients with coeliac disease and in a group of healthy controls, evaluating the strength of the observed associations by measuring the aetiologic fractions. Among the antigens significantly associated with coeliac disease, MB2 (DQw2) showed an aetiologic fraction higher than those of DR3 and DR7. Our results suggest that MB2, as associated more frequently than other specificities with a hypothetical disease predisposing gene, may play a role in the pathogenesis of coeliac disease. The significant association of DR3 and DR7 with coeliac disease may be ascribed to linkage disequilibrium of these antigens with MB2. A number of immunologic diseases have been reported in association with HLA-DR antigens which are retarded as human homologues of murine Ta antigens. Recently increasing evidence has suggested that two additional series of Ta genes code for two additional series of Ia antigens termed MB2 and MT.3 Little is known about the association of these newly defined antigens and disease, but MB1 and MT2 have been reported associated with systemic lupus erythematosus4 and primary sicca syndrome.5 Moreover, it is noteworthy that the association between MB1 and systemic lupus erythematosus4 and between MT2 and primary sicca syndrome5 has been shown to be stronger than those between DR antigens and the above mentioned conditions. These clinical studies suggest that MB and MT antigens may be more important than DR in genetic predisposition to some diseases. In view of this we have studied the frequency of MB and MT antigens in coeliac disease, a condition known to be associated with DR alleles DR3 and DR7.6 Methods PATIENTS Fifty one biopsy proven coeliac patients (aged 15-68 years, mean 38-7 years) were typed for DR and MT antigens. The control group was made up of 56
We measured splenic function using a simple, non-isotopic method in childhood coeliac disease. No... more We measured splenic function using a simple, non-isotopic method in childhood coeliac disease. No patients were shown to have hyposplenism. This has important clinical and therapeutic implications.
EDITOR vs 5). Among reflux patients, the PT4 was always higher in the supine position than in the... more EDITOR vs 5). Among reflux patients, the PT4 was always higher in the supine position than in the upright position (44 vs 10% for nAR and 34 vs 10% for AR patients). This difference was significant (P < 0.05). Peptide Levels. No significant difference was evident for peptide between the four (nAnR, nAR, AnR and AR) groups of patients studied (Table 1). Peptide Integrated Response to Test Meal. As was the case for the basal hormone levels, the integrated response to the test meal did not differ between the four groups of patients (Table 1) regardless of the peptide being considered. These results suggest strongly that alterations in basal or food-stimulated plasma levels of motilin, cholecystokinin, somatostatin, gastrin, or neurotensin are not causally related with asthma in patients with gastroesophageal reflux.
Ninety patients whose spleen had been removed either because of trauma (41 cases) or as an electi... more Ninety patients whose spleen had been removed either because of trauma (41 cases) or as an elective procedure (49) were investigated for return of splenic function by counting pitted red cells and examining spleen scans made after injection of heat damaged 99mTc labelled red cells. There was no significant difference in the proportion of pitted red cells between the two groups of patients. Evidence of splenic tissue in scintiscans was not invariably associated with low pitted 'red cell values, suggesting that the presence of splenic tissue did not necessarily mean return of splenic function. In every patient whose proportion of pitted red cells was less than 16.2% the scintiscan showed splenic uptake. The proportion of patients with pitted red cell values below 16 2% was significantly higher in the group operated on for trauma, and it is concluded that this was due to splenosis. A high inverse correlation between pitted red cell counts and computed splenic volumes was found. Patients with pitted red cell values of less than 16 2% had computed volumes of 22-133 cm3; below this range the proportion of pitted red cells rose very sharply. These results confirm that splenosis occurs in adults, though less often than in children, and suggest that when splenic tissue is to be implanted a graft of at least 20-30 cm3 is needed to ensure satisfactory return of splenic function.
erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, whi... more erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, which may be accompanied by acute phase reactants. The relationship between EHOA and classical osteoarthritis (OA) is still controversial, since some authors consider EHOA as a distinct disease, other as a subset of OA, and some as a border entity between OA and rheumatoid arthritis (RA). Scarce data are available about the seroimmunological profile of the disease, which could aid to identify a possible role of the immune system in EHOA pathogenesis, and could also allow to better differentiate EHOA both from OA and RA. blood was drawn from the following patients: 37 with EHOA, 35 with OA and 45 with RA. All sera were tested for rheumatoid factor, anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), anti-extractable nuclear antigens (anti-ENA) and anti-neutrophil cytoplasmic antibodies (ANCA). ANCA were never detected in OA, whereas they were found in 7 (19...
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