Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, ... more Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma a-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.
Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp... more Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype–related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis betwe...
Sensitive and highly specific ELISA assays were developed to determine humoral immune response ag... more Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies from the authors' laboratory have shown that major depression is accompanied by significa... more Studies from the authors' laboratory have shown that major depression is accompanied by significantly increased plasma concentrations of positive acute-phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular variation with three known phenotypes (Hp I-1, Hp 2-1, and Hp 2-2). This study investigated haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. Method: Haptoglobin plasma levels of 22 healthy volunteers, 32 patients with minor depression, and 72 patients with major depression were determined by means of a laser nephelometric method. Haptoglobin phenotyping ofthese 126 subjects and 200 healthy blood donors was also carried out. Results: The patients with major depression exhibited significantly higher haptoglobin plasma levels than the healthy comparison subjects and the patients with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1 carriers. The frequencies ofhaptoglobin phenotypes Hp 2-1 (61. 1 %) and Hp 2-2 (20.8%) in the patients with major depression were significantly higher and lower, respectively, than the frequencies in the normal population (i.e., the blood donors: 48.0% and 37.0%, respectively). The frequency ofthe Hp-i gene was significantly greater in the patients with major depression (48.6%) than in the normal population (39.0%). Conclusions: Major depression is characterized by a hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This altered distribution of haptoglobin phenotypes and genes suggests that genetic variation on chromosome 1 6 may be associated with that illness.
To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MR... more To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group (IMWG) response criteria. The retrospective study includes 27 newly diagnosed patients, providing 99 MRI-investigations. Patients were categorized according to the IMWG response criteria. Quantitative assessment was based on signal intensities (SI) of T1-weighted, fat-saturated T2-weighted and b1000 images, apparent diffusion coefficients (ADC) and parameters from time-intensity-curves (TIC) derived from L3. Qualitative visual analysis of conventional MRI-images, b1000-images and TICs, providing a "combined skeletal score", was used to create MRI response criteria. The combined skeletal score could significantly differentiate between subgroups based on IMWG response criteria (p=0.016). The gold standard plasmacytosis could significantly differentiate between subgroups based on MRI response criteria (p<0.001), as well as slope (p<0.001) and ADC (p=0.006). There is a good agreement between IMWG and MRI response criteria (Kendall's coefficient=0.761). Response evaluation of MM-patients based on the combination of anatomical information from conventional MRI with functional information from DCE-MRI and DWI, is useful for monitoring therapy.
Background: A hitherto undescribed form of diabetes mellitus type 2 is reported in a Flemish fami... more Background: A hitherto undescribed form of diabetes mellitus type 2 is reported in a Flemish family. In these patients, markedly elevated gastrin levels were observed, which could not be linked to gastrointestinal symptoms. Materials and methods: Gel permeation chromatography was performed for gastrin, insulin, and proinsulin. Proprotein convertase subtilisin/kexin type (PCSK1 and PCSK2)] were sequenced. Whole-exome sequencing was performed on the genomic DNA extracted from leukocytes of the proband of the family. Results: Gel permeation chromatography revealed that the apparent hypergastrinemia was caused by the accumulation of biologically inactive progastrin. Besides, high serum concentrations of proinsulin and intact fibroblast growth factor 23 (FGF23) were also detected. Sequencing of PCSK1 and PCSK2 genes did not reveal any mutations in these genes. Whole exome sequencing revealed a c.1150C>T (p.Pro384Ser) mutation in G protein-coupled receptor kinase 6 (GRK6), which cosegregated with the disease. Expression of the mutant enzyme in mammalian cells revealed that it was mislocalized compared to the wild-type GRK6. Conclusions: In the affected patients, prohormone processing is impaired likely due to the altered function of mutant GRK6. Delayed pro-insulin processing causes hypoglycaemia episodes a couple of hours following meals. In addition, increased plasma concentrations of progastrin and intact FGF23 in the affected individuals can be explained by incomplete processing of the precursor hormones.
With interest, we read the paper of Teama et al. 1 which investigated the association between vit... more With interest, we read the paper of Teama et al. 1 which investigated the association between vitamin D concentrations and the severity of coronavirus disease 2019 (COVID-19). More specifically, a high frequency of hypovitaminosis D in severe COVID-19 patients was observed, suggesting a potential association between vitamin D deficiency and a poor disease outcome. Despite the correlation between vitamin D deficiency and severe COVID-19, the potential protective role of vitamin D against severe COVID-19, based on its influence on both adaptive and innate immunity, remains unclear. 2 We would like to discuss the potential influence of vitamin D binding protein (DBP) and its polymorphisms on the reported results. DBP is the major serum transporter and reservoir of all circulating vitamin D metabolites. In healthy subjects, ∼85% of the vitamin D metabolites are bound with high affinity to DBP, whereas albumin binds ∼15% with low affinity. This member of the albumin and alpha-fetoprotein gene family is characterized by a considerable polymorphism with three major alleles determined by the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 [DBP1F (rs7041-T/rs4588-C), DBP1S (rs7041-G/rs4588-C), and DBP2
International Conference on Control and Automation, 2017
Background: Histidine-containing dipeptides such as carnosine and anserine are protective towards... more Background: Histidine-containing dipeptides such as carnosine and anserine are protective towards development of diabetic nephropathy in rodents. In humans, these dipeptides are hydrolyzed by the enzyme serum carnosinase 1 (hCN1), hindering the protective properties of these dipeptides, especially in people with high CN1 activity. Physical exercise is thought to enhance the levels of circulating
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SAR... more Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently invoking a pandemic with a huge medical and financial impact. One of the striking features of this pandemic is the considerable variation in disease presentation and severity amongst patients, ethnic groups, and countries. This variation can be partially explained by differences in population density, demographic factors (age, sex) and comorbidities (e.g. hypertension, obesity and diabetes mellitus). Also, genetic factors likely contribute to SARS-CoV-2 infection risk and/or COVID-19 development. SARS-CoV-2 host cell attachment, the first step in the host cell entry process, is predominantly facilitated by the angiotensin-converting enzyme 2 (ACE2) receptor [1, 2]. ACE2 is part of the ACE2/ angiotensin-(1-7)/Mas axis and counteracts the effects of its homologue ACE1, which is involved in the ACE1/angiotensin II/angiotensin I receptor axis of the renin-angiotensin-aldosterone system (RAAS). An ACE1/ACE2 imbalance has been suggested to play an important role in SARS-CoV-2 infectivity and COVID-19 progression [3]. The ACE1 gene is characterised by a genetic deletion/insertion (D/I) of an alu repeat in intron 16 and this polymorphism (rs1799752) shows an important geographical variation [4]. Strikingly, 60% of ACE1 levels in blood seem to be determined by this D/I polymorphism [5, 6]. This profound influence can be explained by the presence of two different promotors and alternative splicing resulting in two isoforms of the gene [7]. Since ACE1 and ACE2 levels are strongly regulated by common genetic variants in their genes [3], ACE2 levels may also be influenced by this polymorphism. Recently, we showed that COVID-19 incidence was inversely correlated to the presence of the ACE1 D-allele frequency [8]. Also, a significant correlation between COVID-19 related mortality and the prevalence of the D-allele was observed. Furthermore, other genes associated to RAAS (SLC6A20 and ABO) have been picked up with genome-wide significance for severe COVID-19 with respiratory failure [9]. Interestingly, the ABO-locus modulates a quantitative variation in ACE1 levels [10]. Furthermore, the link between severe COVID-19 and hypertension, diabetes and cardiovascular disease raises the hypothesis of genetic predisposition of RAAS genes and severe COVID-19. We determined ACE2 protein expression in the lung tissue of different patient groups (patient characteristics are shown in figure 1a) [11]. Briefly, ACE2 protein expression was visualised by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded lung tissue blocks using anti-ACE2 antibody (Abcam: ab15348; isotype: Rabbit IgG, R&D systems, AB-150-C) and quantitative measurements of the ACE2-positive signal in alveolar tissue were performed using Axiovision software (Zeiss, Oberkochen, Germany). Representative images of the ACE2 IHC staining (including isotype control) are @ERSpublications Increased protein levels of ACE2 in alveolar epithelium of subjects who are homozygous for the ACE1 insertion of rs1799752 might facilitate host cell entry of #SARSCoV2 and explain the higher prevalence of #COVID19 in certain regions https://bit.ly/3k6aAE8 Cite this article as: Jacobs M, Lahousse L, Van Eeckhoutte HP, et al. Effect of ACE1 polymorphism rs1799752 on protein levels of ACE2, the SARS-CoV-2 entry receptor, in alveolar lung epithelium.
CoV-2, more especially those with the DBP 1F/2 or 2/2 phenotype. As there is an overlap between r... more CoV-2, more especially those with the DBP 1F/2 or 2/2 phenotype. As there is an overlap between risk factors for severe COVID-19 and vitamin D deficiency, including obesity, older age, and Black or Asian ethnic origin, randomized controlled trials testing vitamin D supplementation in the treatment of COVID-19 are in progress. 12 In these trials, we suggest taking the DBP genetic variability into account as polymorphisms have been identified as significant factors affecting childhood 25-hydroxyvitamin D status. These data could lead to more individualized medicine concerning the recommended vitamin D daily allowance, taking into account racially/ethnically associated disparities in children. 10 CONFLICT OF INTERESTS The author declares that there are no conflict of interests. AUTHOR CONTRIBUTIONS Marijn M. Speeckaert and Joris R. Delanghe have written, reviewed, and edited the manuscript.
Although giant cell arteritis, also called temporal arteritis, is the most common primary vasculi... more Although giant cell arteritis, also called temporal arteritis, is the most common primary vasculitis in the elderly, an association with AA amyloidosis has rarely been reported. AA amyloidosis is a disorder that results from the extracellular deposition of proteolytic cleavage products of serum amyloid A, which occurs in the setting of long-standing inflammation. We present a case of a patient with giant cell arteritis who developed a rapidly deteriorating kidney function, due to AA amyloidosis. Early recognition of this rare phenomenon is crucial as prompt treatment may be beneficial in the salvage of renal function.
• GHF is a common phenomenon in the pediatric ICU, especially in the youngest children and those ... more • GHF is a common phenomenon in the pediatric ICU, especially in the youngest children and those not on vasopressor support. • We recommend using an age dependent definition of GHF, related to renal maturation processes.
We tested whether them is a synergistic unterachon hehvOen these two mechamsms On promoting throm... more We tested whether them is a synergistic unterachon hehvOen these two mechamsms On promoting thrombosis On e m~btt model of atlenal lhmmbus fen'nation, Methods: Carotid arlery was inslrumontoO with Doppler flow probe and a rmodlo ele~rodo. Pallmlly oocluswO thmmbus was formed by applymg 150 , A Of current which damages the endothehum Alter d0velopment Of 50% Of the arte~f by throml~, the cummt was stopped and a munne
Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, ... more Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma a-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.
Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp... more Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype–related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis betwe...
Sensitive and highly specific ELISA assays were developed to determine humoral immune response ag... more Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies from the authors' laboratory have shown that major depression is accompanied by significa... more Studies from the authors' laboratory have shown that major depression is accompanied by significantly increased plasma concentrations of positive acute-phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular variation with three known phenotypes (Hp I-1, Hp 2-1, and Hp 2-2). This study investigated haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. Method: Haptoglobin plasma levels of 22 healthy volunteers, 32 patients with minor depression, and 72 patients with major depression were determined by means of a laser nephelometric method. Haptoglobin phenotyping ofthese 126 subjects and 200 healthy blood donors was also carried out. Results: The patients with major depression exhibited significantly higher haptoglobin plasma levels than the healthy comparison subjects and the patients with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1 carriers. The frequencies ofhaptoglobin phenotypes Hp 2-1 (61. 1 %) and Hp 2-2 (20.8%) in the patients with major depression were significantly higher and lower, respectively, than the frequencies in the normal population (i.e., the blood donors: 48.0% and 37.0%, respectively). The frequency ofthe Hp-i gene was significantly greater in the patients with major depression (48.6%) than in the normal population (39.0%). Conclusions: Major depression is characterized by a hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This altered distribution of haptoglobin phenotypes and genes suggests that genetic variation on chromosome 1 6 may be associated with that illness.
To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MR... more To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group (IMWG) response criteria. The retrospective study includes 27 newly diagnosed patients, providing 99 MRI-investigations. Patients were categorized according to the IMWG response criteria. Quantitative assessment was based on signal intensities (SI) of T1-weighted, fat-saturated T2-weighted and b1000 images, apparent diffusion coefficients (ADC) and parameters from time-intensity-curves (TIC) derived from L3. Qualitative visual analysis of conventional MRI-images, b1000-images and TICs, providing a "combined skeletal score", was used to create MRI response criteria. The combined skeletal score could significantly differentiate between subgroups based on IMWG response criteria (p=0.016). The gold standard plasmacytosis could significantly differentiate between subgroups based on MRI response criteria (p<0.001), as well as slope (p<0.001) and ADC (p=0.006). There is a good agreement between IMWG and MRI response criteria (Kendall's coefficient=0.761). Response evaluation of MM-patients based on the combination of anatomical information from conventional MRI with functional information from DCE-MRI and DWI, is useful for monitoring therapy.
Background: A hitherto undescribed form of diabetes mellitus type 2 is reported in a Flemish fami... more Background: A hitherto undescribed form of diabetes mellitus type 2 is reported in a Flemish family. In these patients, markedly elevated gastrin levels were observed, which could not be linked to gastrointestinal symptoms. Materials and methods: Gel permeation chromatography was performed for gastrin, insulin, and proinsulin. Proprotein convertase subtilisin/kexin type (PCSK1 and PCSK2)] were sequenced. Whole-exome sequencing was performed on the genomic DNA extracted from leukocytes of the proband of the family. Results: Gel permeation chromatography revealed that the apparent hypergastrinemia was caused by the accumulation of biologically inactive progastrin. Besides, high serum concentrations of proinsulin and intact fibroblast growth factor 23 (FGF23) were also detected. Sequencing of PCSK1 and PCSK2 genes did not reveal any mutations in these genes. Whole exome sequencing revealed a c.1150C>T (p.Pro384Ser) mutation in G protein-coupled receptor kinase 6 (GRK6), which cosegregated with the disease. Expression of the mutant enzyme in mammalian cells revealed that it was mislocalized compared to the wild-type GRK6. Conclusions: In the affected patients, prohormone processing is impaired likely due to the altered function of mutant GRK6. Delayed pro-insulin processing causes hypoglycaemia episodes a couple of hours following meals. In addition, increased plasma concentrations of progastrin and intact FGF23 in the affected individuals can be explained by incomplete processing of the precursor hormones.
With interest, we read the paper of Teama et al. 1 which investigated the association between vit... more With interest, we read the paper of Teama et al. 1 which investigated the association between vitamin D concentrations and the severity of coronavirus disease 2019 (COVID-19). More specifically, a high frequency of hypovitaminosis D in severe COVID-19 patients was observed, suggesting a potential association between vitamin D deficiency and a poor disease outcome. Despite the correlation between vitamin D deficiency and severe COVID-19, the potential protective role of vitamin D against severe COVID-19, based on its influence on both adaptive and innate immunity, remains unclear. 2 We would like to discuss the potential influence of vitamin D binding protein (DBP) and its polymorphisms on the reported results. DBP is the major serum transporter and reservoir of all circulating vitamin D metabolites. In healthy subjects, ∼85% of the vitamin D metabolites are bound with high affinity to DBP, whereas albumin binds ∼15% with low affinity. This member of the albumin and alpha-fetoprotein gene family is characterized by a considerable polymorphism with three major alleles determined by the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 [DBP1F (rs7041-T/rs4588-C), DBP1S (rs7041-G/rs4588-C), and DBP2
International Conference on Control and Automation, 2017
Background: Histidine-containing dipeptides such as carnosine and anserine are protective towards... more Background: Histidine-containing dipeptides such as carnosine and anserine are protective towards development of diabetic nephropathy in rodents. In humans, these dipeptides are hydrolyzed by the enzyme serum carnosinase 1 (hCN1), hindering the protective properties of these dipeptides, especially in people with high CN1 activity. Physical exercise is thought to enhance the levels of circulating
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SAR... more Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently invoking a pandemic with a huge medical and financial impact. One of the striking features of this pandemic is the considerable variation in disease presentation and severity amongst patients, ethnic groups, and countries. This variation can be partially explained by differences in population density, demographic factors (age, sex) and comorbidities (e.g. hypertension, obesity and diabetes mellitus). Also, genetic factors likely contribute to SARS-CoV-2 infection risk and/or COVID-19 development. SARS-CoV-2 host cell attachment, the first step in the host cell entry process, is predominantly facilitated by the angiotensin-converting enzyme 2 (ACE2) receptor [1, 2]. ACE2 is part of the ACE2/ angiotensin-(1-7)/Mas axis and counteracts the effects of its homologue ACE1, which is involved in the ACE1/angiotensin II/angiotensin I receptor axis of the renin-angiotensin-aldosterone system (RAAS). An ACE1/ACE2 imbalance has been suggested to play an important role in SARS-CoV-2 infectivity and COVID-19 progression [3]. The ACE1 gene is characterised by a genetic deletion/insertion (D/I) of an alu repeat in intron 16 and this polymorphism (rs1799752) shows an important geographical variation [4]. Strikingly, 60% of ACE1 levels in blood seem to be determined by this D/I polymorphism [5, 6]. This profound influence can be explained by the presence of two different promotors and alternative splicing resulting in two isoforms of the gene [7]. Since ACE1 and ACE2 levels are strongly regulated by common genetic variants in their genes [3], ACE2 levels may also be influenced by this polymorphism. Recently, we showed that COVID-19 incidence was inversely correlated to the presence of the ACE1 D-allele frequency [8]. Also, a significant correlation between COVID-19 related mortality and the prevalence of the D-allele was observed. Furthermore, other genes associated to RAAS (SLC6A20 and ABO) have been picked up with genome-wide significance for severe COVID-19 with respiratory failure [9]. Interestingly, the ABO-locus modulates a quantitative variation in ACE1 levels [10]. Furthermore, the link between severe COVID-19 and hypertension, diabetes and cardiovascular disease raises the hypothesis of genetic predisposition of RAAS genes and severe COVID-19. We determined ACE2 protein expression in the lung tissue of different patient groups (patient characteristics are shown in figure 1a) [11]. Briefly, ACE2 protein expression was visualised by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded lung tissue blocks using anti-ACE2 antibody (Abcam: ab15348; isotype: Rabbit IgG, R&D systems, AB-150-C) and quantitative measurements of the ACE2-positive signal in alveolar tissue were performed using Axiovision software (Zeiss, Oberkochen, Germany). Representative images of the ACE2 IHC staining (including isotype control) are @ERSpublications Increased protein levels of ACE2 in alveolar epithelium of subjects who are homozygous for the ACE1 insertion of rs1799752 might facilitate host cell entry of #SARSCoV2 and explain the higher prevalence of #COVID19 in certain regions https://bit.ly/3k6aAE8 Cite this article as: Jacobs M, Lahousse L, Van Eeckhoutte HP, et al. Effect of ACE1 polymorphism rs1799752 on protein levels of ACE2, the SARS-CoV-2 entry receptor, in alveolar lung epithelium.
CoV-2, more especially those with the DBP 1F/2 or 2/2 phenotype. As there is an overlap between r... more CoV-2, more especially those with the DBP 1F/2 or 2/2 phenotype. As there is an overlap between risk factors for severe COVID-19 and vitamin D deficiency, including obesity, older age, and Black or Asian ethnic origin, randomized controlled trials testing vitamin D supplementation in the treatment of COVID-19 are in progress. 12 In these trials, we suggest taking the DBP genetic variability into account as polymorphisms have been identified as significant factors affecting childhood 25-hydroxyvitamin D status. These data could lead to more individualized medicine concerning the recommended vitamin D daily allowance, taking into account racially/ethnically associated disparities in children. 10 CONFLICT OF INTERESTS The author declares that there are no conflict of interests. AUTHOR CONTRIBUTIONS Marijn M. Speeckaert and Joris R. Delanghe have written, reviewed, and edited the manuscript.
Although giant cell arteritis, also called temporal arteritis, is the most common primary vasculi... more Although giant cell arteritis, also called temporal arteritis, is the most common primary vasculitis in the elderly, an association with AA amyloidosis has rarely been reported. AA amyloidosis is a disorder that results from the extracellular deposition of proteolytic cleavage products of serum amyloid A, which occurs in the setting of long-standing inflammation. We present a case of a patient with giant cell arteritis who developed a rapidly deteriorating kidney function, due to AA amyloidosis. Early recognition of this rare phenomenon is crucial as prompt treatment may be beneficial in the salvage of renal function.
• GHF is a common phenomenon in the pediatric ICU, especially in the youngest children and those ... more • GHF is a common phenomenon in the pediatric ICU, especially in the youngest children and those not on vasopressor support. • We recommend using an age dependent definition of GHF, related to renal maturation processes.
We tested whether them is a synergistic unterachon hehvOen these two mechamsms On promoting throm... more We tested whether them is a synergistic unterachon hehvOen these two mechamsms On promoting thrombosis On e m~btt model of atlenal lhmmbus fen'nation, Methods: Carotid arlery was inslrumontoO with Doppler flow probe and a rmodlo ele~rodo. Pallmlly oocluswO thmmbus was formed by applymg 150 , A Of current which damages the endothehum Alter d0velopment Of 50% Of the arte~f by throml~, the cummt was stopped and a munne
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