IgA Antigliadin Research Articles

The use of anti-transglutaminase and anti-gliadin antibodies to compare the effect of gluten active and gluten-free diet patients suffering from celiac disease in child and adult

Celiac disease is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. The current study aimed to compare the levels of these antibodies in celiac disease patients on active gluten-containing diets and those on gluten-free diets to demonstrate the ability to get rid of Celiac Disease by Gluten-Free Diet. The study involved 100 participants, divided into 60 CD patients and 40 controls, where all participant match in age and gender. The patient group was further divided into two subgroups 40 active celiac and 20 GFD. Blood samples were obtained from all participants, and levels of anti-tTG and anti-gliadin antibodies were using Enzyme-Linked Immunosorbent Assay (ELISA) technology. The results showed The F test indicated a significant difference in the levels of anti-tTG and anti-gliadin antibodies between the active group (G1) and the diet group (G2) in comparison to the control group (G3), with a p-value less than 0.001. Upon conducting a deeper analysis using the least significant difference (LSD) on on anti-tTG IgA and IgG indicate that there are no significant differences between the patient groups G1 and G2, as evidenced by p-values of 0.120 for IgA. However, a significant difference was observed between G1 and G2 for IgG, with a p-value of 0.018. When comparing G1 with G3, and G2 with G3, significant differences were observed, with p-values less than 0.001. In the case of anti-gliadin IgA and IgG, the LSD test revealed a highly significant difference between G1 and G2, as indicated by a p-value less than 0.001. However, no significant differences were found between G1 and G3, with p-values of 0.499 for IgA and 0.110 for IgG. A highly significant difference was none the less observed between G2 and G3, with a p-value less than 0.001.In conclusion, This study highlights the importance of dietary adherence in celiac disease management. Patients on gluten-free diets had significantly lower levels of anti-TG and anti-gliadin antibodies, indicating better control of the autoimmune response. Monitoring these antibody levels can be a valuable tool in assessing the effectiveness of dietary interventions in celiac disease patients.

Screening of celiac disease in children with growth failure

Celiac disease is a chronic enteropathy caused by intolerance to gluten. Its clinical spectrum is broad. Presentation of celiac disease varies from absence of symptoms to gastrointestinal (classic) and/or extraintestinal (non-classic) symptoms. Patients without symptoms may have latent or silent celiac disease. Because celiac disease can be atypical or even clinically silent, many patients remain undiagnosed and at risk for the long-term, sometimes serious complications of untreated celiac disease.The aim of this study is to determine the prevalence of celiac disease (CD) in children with growth failure and the diagnostic value of tissue-transglutaminase (TTG) IgA antibodies and IgA antigliadin antibodies (AGA) for celiac disease.Patients and Methods: A total of 104 children (43 male, 61 female) with growth failure without a specific etiology were studied. Extensive investigations had shown no abnormalities in any subject. Anthropometric parameters and IgA AGA and IgA TTG antibodies were evaluated in this study group. These antibodies were measured by enzyme-linked immunosorbent assay. All patients were referred for an endoscopic intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria .Results: the prevalence of properly diagnosed CD among patients with growth failure in this study was 25.9% (27 of 104patients).Out of 104 patients 57 of them were positive upon screening with the serological tests. IgA -AGA, and IgA -TTG antibodies were found in 81.4% (n = 22 out of 27 with confirmed CD), and 88.8% (n = 24 out of 27 with confirmed CD) of patients with growth failure, respectively. Sensitivity,Specificity ,the positive predictive value (PPV),negative predictive value(NPV) for TTG antibodies were found to be 88.8%, 94.2%, 85.7%, and 94.7% for CD in the group of patients with growth filure in this study and for IgA AGA: sensitivity 81.4%, specificity 88.4%, positive predictive value( PPV) 75.8%, negative predictive value (NPV) 90.6% were found in this study.Conclusion: We conclude that the prevalence of celiac disease is high in patients with idiopathic growth failure and it is important to test all children with idiopathic growth failure for celiac disease by measuring serologic markers and performing an intestinal biopsy.

Common Autoimmune Antibodies in Unexplained Infertile Female Patients in Saudi Arabia.

Unexplained female infertility is a devastating health problem that has become increasingly prevalent worldwide with no specific explanation despite comprehensive evaluations. Recent data suggestthat serum autoimmune antibodies are frequently found in patients with unexplained female infertility. This study aims to identify the prevalence of common autoantibody abnormalities in females with unexplained infertility in Saudi Arabia. A cross-sectional study was conducted on female patients with unexplained infertility sequentially referred to the allergy and immunology clinic at King Abdulaziz University Hospital (KAUH). Demographics, clinical characteristics, and 12 common autoantibody immunological tests were described as frequency and percentage. The chi-square test was applied to evaluate any associations. A total of 119 females with unexplained infertility were studied; of those, 97 (81.5%) had secondary infertility. Their average age was 33.9 ± 5.6 years ranging from 23 to 49 years. The overall prevalence of a high level of at least one autoantibody (above the normal range) was 84%. The predominant high autoantibodies were antithyroglobulin in 42 (35.3%), antithyroid microsomal in 41 (34.5%), beta 2 glycoprotein IgM in 40 (33.6%), antigliadin IgA in 32 (26.9%), antinuclear in 22 (18.5%), and anticardiolipin IgM in 18 (15.1%) of the participants. The following significant associations were found in our study: secondary infertility with beta 2 glycoprotein (p = 0.022), age with antithyroglobulin (p = 0.027), and the number of pregnancies with anti-tissue transglutaminase IgG and antigliadin IgA(p = 0.015 and p = 0.043, respectively). A high level of at least one autoantibody was detected in the majority of females with unexplained infertility. Antithyroid, antiphospholipid, antigliadin, and antinuclear autoantibodies were the most commonautoantibodies.These findings may encourage autoantibody screening in infertile females to discover any potential immunopathology in further clinical studies.

S3456 Olmesartan-Induced Enteritis: When Symptoms Do Not Improve With Drug Discontinuation

Introduction: Severe diarrhea is a well-known, but rare, complication of Olmesartan. The enteropathy caused by Olmesartan is histologically similar to Celiac disease, however celiac serologies are negative and it lacks a response to a gluten free diet. In most cases, symptoms resolve with the discontinuation of the medication. We present a case of Olmesartan induced enteropathy that only improved after the initiation of budesonide. Case Description/Methods: A 73-year-old female with a history of hypertension presented with complaints of nausea, vomiting and watery diarrhea. Initial workup with bloodwork, stool studies and imaging were all unremarkable. Recent outpatient colonoscopy was unremarkable. Review of her medications did not reveal any typical culprits of microscopic colitis. Given persistent nausea and vomiting, an upper endoscopy was pursued. Celiac serologic testing, including issue transglutaminase (tTg) IgA and IgG, anti-gliadin IgA and anti-endomysial IgA antibodies were all normal. Qualitative IgA levels were within normal limits. Upper endoscopy was performed with duodenal biopsies revealing moderate active chronic duodenitis with blunting of villous architecture and increased intraepithelial lymphocytic infiltrate, suspicious for celiac sprue. At this point, a closer review of her medications revealed a prescription for Olmesartan. Olmesartan was discontinued, however she continued to have significant diarrhea, up to 2.5L daily, for over a week after discontinuation. Given persistent diarrhea, nausea and vomiting, resulting in significant electrolyte abnormalities, the decision was made to initiate Budesonide. She experienced rapid improvement in symptoms after the initiation of Budesonide and only reported two loose stools per day on discharge. (Figure) Discussion: The initial workup for chronic diarrhea involves a thorough medication review. Physicians who prescribe Olmesartan should be aware of the enteropathy it can cause, as it is likely more common than expected. Other drugs such as azathioprine, colchicine, mycophenolate, methotrexate and neomycin have also been implicated in a similar enteropathy. Timely diagnosis can help decrease healthcare utilization and patient discomfort. In cases such as ours, the enteropathy can be severe enough to result in hospital admission. Immunosuppressant’s such as steroids or azathioprine have shown great efficacy in treatment of these refractory cases.Figure 1.: Histology of duodenal biopsy showing (A) Moderate active chronic duodenitis with blunting of villous architecture and (B) Increased intraepithelial lymphocytic infiltrate.

S1705 Celiac Disease and Chronic Pancreatitis

Introduction: Celiac disease involves a T-cell-mediated immune response to dietary gluten. Celiac disease has 3-fold increased risk for developing chronic pancreatitis but only has a reported incidence of 0.52%. We present a case of a 61-year-old male with newly diagnosed celiac disease who was incidentally found to have associated chronic pancreatitis. Case Description/Methods: A 61-year-old male with a past medical history of diabetes, hypertension, coronary artery disease, and a remote history of hepatitis presented to our clinic for his first screening colonoscopy and recent anemia. Prior to colonoscopy, the patient noted a 45-pound unintentional weight loss over the past few years, and with recent lab studies revealing a hemoglobin level of 11.7 g/dL. The patient then underwent colonoscopy, esophagogastroduodenoscopy (EGD), and an extensive laboratory work-up that was significant for iron deficiency anemia, anti-gliadin (AGA) IgA >150 U/mL, AGA-IgG 134 U/mL, endomysial (EMA)-IgA positive, tissue transglutaminase (tTG)-IgA >100 U/mL, total IgA 280 mg/dL, fecal elastase 31 mcg/g and was positive for anti-smooth muscle antibodies (1:160). Subsequent results were negative for viral hepatitis panel, antinuclear antibodies, anti-mitochondrial antibodies, alpha-1 antitrypsin levels, and normal ceruloplasmin levels. Colonoscopy was unrevealing except for a diminutive tubular adenoma. EGD later revealed blunted villi with flat mucosa in the first and second portion of the duodenum. Biopsy results later confirmed pathology results compatible with celiac disease. During this course of workup, the patient developed nephrolithiasis and with incidental findings of pancreatic atrophy and pancreatic head calcifications detected on CT urogram. Chronic pancreatitis was later confirmed on endoscopic ultrasound with evidence of multiple intraductal stones. Patient did not have a history of alcohol use or pancreatic problems in the family. After being diagnosed with Celiac disease and secondary chronic pancreatitis with exocrine pancreatic insufficiency, he was started on a gluten-free diet and pancrelipase. Patient was noted to have 9-pound weight gain during a 4 month follow-up appointment. Discussion: Chronic pancreatitis is a rare extraintestinal manifestation of celiac disease, reported to have a threefold increased risk but only with a reported incidence of 0.52% at least 30 days after diagnosis of celiac disease compared to 0.13% in non-celiac disease patients.

A10 EARLY LIFE SENSITIZATION TO GLUTEN INDUCES SUSTAINED IMMUNOPATHOLOGY IN DR3-DQ2 MICE

Abstract Background Celiac disease (CeD) is an autoimmune T-cell mediated enteropathy, triggered by gluten, a group of proteins found in wheat, barley, and rye. The defined role of gluten as a dietary trigger, necessary genes (HLA-DQ2 and/or DQ8), and tissue transglutaminase (TG2) as the autoantigen together, are unique features of CeD. Although CeD onset can occur at any age, first dietary introduction of gluten during infancy is a critical window of exposure, especially in infants homozygous for the HLA DQ2.5 allele. While adult sensitization studies have been recently performed in DR3-DQ2 mice, the consequences of early life gluten sensitization timing remain unexplored. Aims Our aim was to characterize gluten-immunopathology and CeD-specific serology in specific pathogen free (SPF) DR3-DQ2 transgenic mice sensitized to gluten, 1 week before weaning. Methods Seven-week-old SPF DR3-DQ2 transgenic mice, kept on a gluten-free diet (GFD), were paired for breeding. At post-natal day 3, pups were standardized to 4 per litter (n=2 male, n=2 female) to ensure equal nutrition across litters. At 14 days of age, pups were sensitized with pepsin-trypsin digested gliadin and cholera toxin (CT) three times in one week (n=15). At 21 days of age, pups were weaned and placed either on a gluten-containing diet (n=7), (equivalent of 20g/d of gluten in a human diet -high dose-) or an isocaloric GFD (n=8) until 10 weeks of age. Non-sensitized controls (n=7) received only CT and were kept on the GFD. At sacrifice, serum was collected for anti-TG2 and anti-gliadin antibodies (AGA). Jejunal tissue was collected for histological analysis using villus-to-crypt (V/C) ratios and CD3+ intraepithelial lymphocytes (IEL) counts. Results Gluten-sensitized mice placed on a gluten-containing diet post-weaning had lower V/C ratios and higher CD3+ IEL counts compared with controls (p<0.01). Pre-weaning sensitized mice that were kept on a GFD post-weaning had sustained decreases in V/C ratios and higher CD3+ IEL counts (p<0.01). Out of 15 sensitized mice, 7 developed positive anti-gliadin IgA (p=0.02) and 4 had positive anti-TG2 IgA antibodies (p=0.01) in intestinal contents, irrespective of gluten in the diet. None of the controls had detectable AGA or anti-TG2 antibodies. Conclusions Pre-weaning gluten sensitization of DR3-DQ2 mice induced prolonged gluten immunopathology that did not reverse after 5 weeks on a GFD. Our results indicate that young DR3-DQ2 mice are susceptible to gluten sensitization, with sustained immunopathology, suggesting a critical window of vulnerability in familial carriers of DQ2.5. This novel model will be useful to investigate environmental cofactors at the first time of gluten introduction to the diet. Funding Agencies CIHR

Association between Diabetes Mellitus Type-1 and Celiac Disease in Growth Retardation Iraqi Patients

This study was performed in the ministry of health- Specialized Center for Endocrinology and Diabetes in Baghdad. Measurement of some biochemical parameters in serum of 93 patients with growth retardation divided into two groups: group-1 (G1) control group without diabetes, and group-2 (G2) with diabetes. The results showed that celiac disease reduces weight and consequently body mass index. The Anti-tissue and Anti-Gliadin IgA increase significantly (p˂0.01) in G2 compared with G1, were the Anti-tissue IgA titer reached 6.88 and 65.30 U/ml and Anti-Gliadin IgA titer reached 7.69 and 72.29 U/ml in G1 and G2 respectively. In addition, the results express positive linear relationship (p ˂ 0.01) among glucose level with Anti-tissue and Anti-Gliadin IgA in G2, using the regression equation of Anti-tissue and Anti-Gliadin y=4.327+0.199 (S. glucose) and y=6.027+0.102 (S. glucose) respectively.

Celiac Disease.

Celiac Disease.

Organ-specific autoimmune markers in adult patients with type 1 diabetes mellitus.

We aimed to investigate the presence of thyroid, celiac disease (CD) and anti-parietal cell antibodies (APCA) in adult type 1 diabetes (T1DM) patients. Data of 287 T1DM patients >16years old were reviewed retrospectively. Thyroid disease related, CD related antibodies and APCA were evaluated. Patients were divided into early onset (<30years old) and late-onset (≥30years old) TIDM, and ≤10years, 11-20years and >20years according to disease duration. There were 142 (49.5%) female and 145 (50.5%) male patients. The median age at diagnosis and disease duration were 21 (2-53) and 6.91 (0-50.8)years, respectively. Antibody positivity rates were anti-glutamic acid decarboxylase (anti-GAD) 72.8%, anti-insulin 9.1%, anti-islet cell 25.7%, antithyroid peroxidase (anti-TPO) 34.8%, anti-thyroglobulin 19.9%, anti-endomysial IgA (EMA-IgA) 7.6%, anti-gliadin IgA (AGA-IgA), 12.2%, AGA-IgG 13.0%, tissue transglutaminase IgA 7.1% and APCA 14.4%. One hundred twenty-eight (44.6%) patients had at least one non-diabetes autoantibody. Thyroid autoantibodies and dysfunction were significantly higher in women than men. Anti-TPO positivity was higher in the late-onset group (P=.044). Anti-GAD level was correlated with thyroid related antibody positivity in male patients with positive anti-GAD (r: .340, P: .006). The positivity of EMA-IgA and AGA-IgA was higher in patients with disease duration >20years (P=.017 and .039, respectively). Almost half of the adult T1DM patients were positive for at least one non-diabetic antibody. It is important to investigate thyroid autoimmunity in patients diagnosed with T1DM at any age, including advanced age. CD associated antibody positivity increases with disease duration, suggesting that they should be re-evaluated at clinical suspicion, even if prior tests were negative.

Serologic Testing for Celiac Disease in Graves’ Hyperthyroidism: Should We Act Early?

ABSTRACT Background: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves’Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. Materials and Methods: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG – AGA and IgA – AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. Results: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. Conclusion: Due to possibility of false seropositivity of celiac antibodies in patients with Graves’ thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

Microcytic Anemia and Celiac Disease Preceding Pulmonary Symptoms in Lane-Hamilton Syndrome

History and Case PresentationPatient is a 36 year old white male with a history of chronic microcytic anemia and tobacco use. He could not recall any pertinent family history. His chronic anemia started at age 29, at which time he had no pulmonary symptoms. Representative laboratory studies included HGB 7.7 HCT 27.2 MCV 60.7 FE/TIBC of 13/428 with albumin of 3.2. He was diagnosed with iron deficiency, and received multiple intravenous iron infusions. These therapies briefly increased his hematocrit, however, he consistently required PRBC transfusions within 1-2 months of receiving intravenous iron, as he would again become anemic with microcytosis; he estimated that he had received approximately 30 units of PRBCs since age 29. Dyspnea on exertion was first noticed at age 34, which progressively worsened and was associated with occasional episodes of blood tinged sputum and cough, but never frank hemoptysis. Pulmonary function tests in 2016 were reportedly normal, and there were no abnormalities on CXR.Multiple EGDs and colonoscopies were performed without any evidence of bleeding. Duodenal biopsies with villous flattening were first noted in 2014. Patient adhered to a gluten free diet for two months immediately following his diagnosis of celiac sprue and reported that his anemia stabilized, however he stopped the diet for unclear reasons.He presented to our facility in May of 2017 with intermittent sharp chest pain, severe dyspnea on exertion, and lightheadedness. Initial HGB was 7.2 HCT 24.7 MCV 59.2 WBC 6700 PLT 104000. Iron studies obtained prior to transfusion reveal Fe/TIBC of 17/253, ferritin 90, albumin 1.8. Peripheral smear was consistent with iron deficiency, with mild to moderate anisopoikilocytosis. Absolute reticulocyte count the day after admission was 0.104 with HCT of 21.7.He had a similar presentation 8 months prior, in October 2016. CT chest was remarkable for ground-glass opacities, pulmonary fibrosis, emphysema, and mild bilateral hilar adenopathy. There was nephrotic range proteinuria, and albumin was 1.9. He was given ferric gluconate with improvement in his symptoms, and was discharged four days later with HGB of 9.2. He was lost to follow up until May, and did not receive scheduled EBUS and lung biopsy. Repeat CT scan was performed on second admission, showing interval progression of peripheral fibrosis and honeycombing (Image 1).Investigations in 2017 included an EGD/colonoscopy, with single duodenal biopsy finding of increased intraepithelial lymphocytes, with preserved villous architecture, h. pylori negative. Tissue transglutaminase IgA was >250 U/mL and anti-gliadin IgA was 26 U/mL. Genetic testing revealed HLA DQ2 serotype. There was no evidence of CHF or pulmonary HTN on Echo. Hemoglobin electrophoresis revealed no abnormal hemoglobin migration and physiologic HbA2 and HbF levels. B12 and folate levels were within normal limits. Lung biopsy revealed alveolar filling with numerous hemosiderin laden macrophages, in background of alveolar pneumoconiosis and phlebosclerosis, (image 2, high magnification).He was administered PRBCs and ferric gluconate, and discharged with instructions to initiate gluten-free diet, as well undergo renal biopsy to evaluate nephrotic syndrome.DiscussionLane-Hamilton Syndrome (LHS), the association of Idiopathic Pulmonary Hemosiderosis (IPH), celiac disease, and microcytic anemia is an extremely rare clinical entity with 15 worldwide cases described in adults. When patient presented with microcytic anemia, ferritin was consistently in the normal range, while remaining iron studies including Fe/TIBC and transferrin saturation were consistent with iron deficiency when corrected for proteinuria and transferrin loss. Historic CBC and iron studies revealed a clear iron deficiency pattern as described. Parenteral iron infusion did improve hematocrit on multiple presentations, but response was transient. Celiac disease was proven by biopsy and serology. Hemosiderin deposition was found on lung biopsy without a plausible alternate etiology. These features are consistent with known characteristics of LHS. While iron deficiency resistant to iron supplementation has been described without inital pulmonary findings in children with IPH, to our knowledge, iron deficiency with celiac disease preceding the development of IPH by such a long interval has not heretofore been described in adult LHS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Gene Expression of NLRP3 Inflammasome in Celiac Disease of Iraqi Children

Celiac disease (CD) is an autoimmune disorder characterized by chronic inflammation that essentially affects the small intestine and is caused by eating gluten-containing foods. This study sought to determine gene expression of NLRP3 Inflammasome in peripheral blood of Iraqi CD children using quantitative real-time PCR (qRT-PCR) assay. Thirty children with CD (12 males and 18 females) were enrolled in the study and their age range was 3-15 years. The diagnosis of the disease was confirmed by serological examinations and intestinal endoscopy. A control sample of 20 age-matched healthy children was also included. The children were stratified for age, gender, body max index (BMI), histological findings, and marsh classification. Further, the sera were examined for IgA anti-tissue transglutaminase (tTG) antibody, IgA anti-gliadin antibody, and interleukin-1 beta (IL-1β). Based on Marsh classification, the results revealed that the majority of patients (70%) had partial villous atrophy (Marsh Ш 3A), while children with subtotal and total villous atrophy (Marsh III: 3B/3C) were presented with a lower frequency (30.0%). Neither Marsh I nor Marsh II has been observed among the patients studied. Serum levels of anti-tTG and anti-gliadin IgA antibodies were significantly higher in CD children than in control children (73.8 and 31.8 vs. 0.8 U//ml, respectively; p &lt; 0.001). Conversely, IL-1β serum level was decreased in CD children but the difference was not significant (35.5vs. 53.4 pg/ml; p = 0.285). In the case of NLRP3 inflammasome, the Relative Fold Change method (2-∆∆Ct) was used to assess the gene expression. The results revealed that the expression of NLRP3 inflammasome was decreased by 0.594 fold in CD children. In conclusion, the NLRP3 inflammasome was down-regulated in the present sample of CD children, and it was accompanied by a decreased serum level of IL-1β.

Does cystic fibrosis make susceptible to celiac disease?

Patients with cystic fibrosis (CF) have a higher incidence of celiac disease (CD) than the healthy population; however, the actual incidence of coexisting CF and CD is unclear. In this report, we aimed to evaluate the frequency of CD and CF coexistence and to assess the clinical findings of affected patients during follow-up. We conducted a retrospective review of patients with CF to reveal the frequency of CD and also investigated the clinical characteristics and clinical response to gluten-free diet in patients with CD. The incidence of CD in 515 patients with CF was 1.4%. The median age at the time of CF diagnosis was 2 months (1-6 months). CD was diagnosed in six patients with poor weight gain, fatty stools, and low z score for BMI and one patient with poor weight gain despite a high protein and calorie diet and pancreatic enzyme replacement. The median age of CD diagnosis was 8 years (2-12 years). Except for one patient who was recently diagnosed, the other six patients gained weight and their accompanying symptoms resolved after starting a gluten-free diet.Conclusion: CD should be investigated in patients with CF in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. What is Known: • CFTR dysfunction may be a risk factor for CD, due to increased intestinal permeability and intestinal inflammation, pancreatic exocrine insufficiency that results in higher antigen load and increased antibodies against to nutritional antigens such as anti-gliadin IgA antibodies. • Although coexistence of CF and CD are rare in the same patient; there is still no consensus on when children with CF should be screened for CD. What is New: • Physicians should consider the investigation of CD in patients with CF, in the presence of inadequate weight and/or height gain or poor control of malabsorption symptoms despite appropriate and adequate nutritional and enzyme replacement treatment. • CFTR dysfunction has been emphasized to develop susceptibility to CD, and patients with CF who have persistent gastrointestinal symptoms despite appropriate and adequate nutritional and enzyme replacement treatment should be screened for CD.

Serological Tests Assessment in Patients Suspected to have Celiac Disease Attending the Gastroenterology and Hepatology Teaching Hospital in Baghdad

Background: Celiac disease is characterized by small intestinal malabsorption of nutrients after the ingestionof wheat gluten or related proteins from rye and barley, villus atrophy of the small intestinal mucosa, promptclinical and histologic improvement following strict adherence to a gluten-free diet, and relapse when glutenis retaken.Aim of the Study: Evaluation of patients seeking gastroenterology and hepatology teaching hospital/medicalcity/Baghdad with suspected celiac disease regarding serological investigation, histological findings andgenetic testing, to determine sensitivity, specificity, positive predictive value and negative predictive valuefor every test.Patients and Method: The study is a cross sectional descriptive analytic study conducted at the teachinghospital of gastroenterology and hepatology/Baghdad/Iraq during a period from the 1st of February 2018 tothe 1st of April 2019. After thorough history and Clinical examination patients with suspected celiac diseasewere sent for serological investigation (TTG IgA and IgG), (antigliadin IgA and IgG), all patients were sentfor endoscopic examination for duodenal biopsies with subsequent histological assessment. Patients whofailed to be confirmed (positive serology and negative histology or vice versa) were sent either for HLAgenotyping or for IgG Deaminated gliadin peptide. Sensitivity &amp; specificity were measured for each test.Results: A total of 140 suspected celiac disease patients involved in this study. Mean age was 18.9 yearsand ranged from 2 years to 60 years. Male represented 36.4% of the cases while female represented 63.6%.Only 19 patients show positive family history of celiac disease (13.6 %). Regarding associated autoimmunediseases, the majority (111 patients) have no associated diseases (79.3%) while the other patients who haveassociations most of them show positive association with type 1 DM (16.4%).Fifty patients (35.7%) presented with short stature, (25.7%) came with diarrhea. The other symptoms varybetween bloating and distention, unexplained anemia and weight loss. Constipation was seen in one patient.tTG IgA and tTG IgG showed high sensitivity, specificity, positive predictive value and negative predictivevalue while antigliadin antibody failed to show these significant results.Conclusion: The use of serologic markers inceliac is easy, direct, noninvasive and reliableand could be benefit in the diagnosis andmonitoring of the disease. More specifically,both the tTG-IgA/IgG are very good markersin the diagnostis of CD. This study confirmedthe high specificity and sensitivity of tTG, and the low results of AGA, but celiac serology does not replace the biopsy in the diagnosis but is useful as anassistant for diagnosis.

Celiac Disease Complicated by Rhabdomyolysis.

At 37 years old, a patient developed chronic watery diarrhea, generalized pain, severe hypokalemia and elevated creatine kinase levels. She was thought to have rhabdomyolysis due to hypokalemia from chronic diarrhea. No organic cause was found. Her symptoms subsided with potassium correction, but hypokalemia persisted; she visited our hospital at 44 years old. Endoscopy detected prominent atrophy of the intestinal villi. Histology indicated Marsh-Oberhuber type-3b disease. Anti-gliadin and anti-tissue transglutaminase IgA antibody tests were positive. She was diagnosed with celiac disease and started on a gluten-free diet, which improved her symptoms. This report is only the tenth of its kind worldwide.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG

Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P= .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P= .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

Evaluation of Ocular Parameters in Adult Patients with Celiac Disease

ABSTRACT Purpose To evaluate ophthalmic parameters in adult celiac patients Methods This cross-sectional study included 31 celiac patients (58 eyes) and 25 healthy controls (50 eyes). Tear break up time (TBUT), schirmer test were measured; corneal thickness, anterior chamber parameters were obtained using scheimpflug camera; retinal nerve fiber layer thickness (RNFL) evaluated by using spectral domain optical cohorence tomography. Results There were no statistically significant differences between the groups in terms of gender, age, and intraocular pressure (p > .05). Schirmer’s test results and TBUT were significantly lower in celiac patients (p < .001, p < .001). Additionally, the superior RNFL was significantly thinner (p = .017), nasal RNFL thicker (p = .007), and anterior chamber depth larger (p = .037) in celiac patients. The tissue transglutaminase 2 IgA antibody and superior RNFL were negatively correlated (r = −0.394, p = .012). The anterior chamber volume and anti-gliadin IgA antibody were positively correlated (r = 0.369 p = .027). Conclusion Celiac disease affects Schirmer’s test results, TBUT, segmental RNFL thickness, and anterior chamber parameters. Ocular parameters might be affected in celiac disease especially in the presence of high antibody titer.

Impact of Instant Controlled Pressure Drop (DIC) Treatment on Chemical, Functional and Immunological Properties of Wheat Gluten

Instant controlled pressure drop DIC technology is a thermo-mechanical treatment method that combines both mechanical and heat impacts of saturated steam pressure over a short period of time. This study aims to investigate the effect of DIC (100–165 °C for 20–60 s) on chemical, functional and immunological properties of wheat gluten powder using response surface methodology. Chemical properties were studied by Fourier transform infrared spectroscopy, thiol measurement and gel electrophoresis. Protein solubility, emulsifying capacity and foaming ability were evaluated as functional properties. Immunological properties were studied by indirect ELISA. After DIC treatment, wheat gluten became rigid which was due to a significant increase in β-structures. Significant loss of α-helixes and a significant increase in intermolecular β-sheet and the rearrangement of disulfide bonds indicated the denaturation of wheat gluten protein. However, the primary structure was not affected. DIC treatment altered the functional properties. The lowest protein solubility, emulsifying capacity and foaming ability were obtained at the highest DIC treatment conditions (165 °C, 60 s). The immunoreactivity of celiac IgA antigliadin antibodies of DIC wheat gluten depended on the individual patient characteristics. However, we note that the immunoreactivity has increased overall.

GENETIC TESTING IDENTIFIES CAUSE OF ENTEROPATHY AND GROWTH FAILURE IN A 10 YEAR OLD MALE

Introduction Enteropathies with features of celiac disease or inflammatory bowel disease (IBD) should spark consideration of an immunodeficiency when presenting at an early age. Case Description We present a 10-year old male with chronic diarrhea starting at 6 weeks of life, initially improved with TPN, steroids, and cow's milk free diet. By 2 years of age, diarrhea returned, and he required frequent courses of steroids to manage his symptoms. The patient had mild dermatitis and poor growth, with otherwise negative review of systems. Endoscopies found duodenitis with severe villous blunting and pancolitis. Laboratory evaluations were notable for negative anti-enterocyte antibodies, elevated antigliadin and tissue transglutaminase IgA levels, and normal T regulatory (Treg) cells and forkhead box P3 (FOXP3) expression. He was diagnosed with Celiac Disease and years later, Crohn's Disease. His clinical course did not improve with gluten avoidance or various immunomodulators. Eventually, sequencing of the FOXP3 gene was performed, revealing a missense mutation consistent with Immune dysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome. Discussion IPEX is a rare syndrome caused by a mutation in the FOXP3 transcription factor of CD4+ Treg cells. The classic IPEX syndrome includes protracted diarrhea, dermatitis, and endocrinopathies, but phenotypes vary. Endoscopic findings of the IPEX enteropathy can mimic those seen in Celiac Disease and IBD, thus a high index of suspicion should be maintained in select patients with early onset of symptoms. Finally, this case highlights the importance of genetic analysis of the FOXP3 gene itself, as IPEX patients can have normal FOXP3 protein expression and Treg numbers.

Pentraxin 3 and biopsy status in celiac patients.

In our study we explored a possible relationship between PTX3 and CD. Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity. 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3. Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform. PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3.31± 1.27 ng/mL and 3.97 ± 0.54 ng/mL versus 1.06 ± 0.59 ng/mL; P < 0.005), with group 1 (0.76±0.31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0.78, P <0.0001), and group 3 (r =0.63, P < 0.005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0.04; group 3, r=0.24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients. PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response.