IgG tTG Research Articles

IMMUNOLOGICAL STUDY OF SOME BIOMARKER IN CELIAC DISEASE IN BASRAH PROVINCE

Objective: This study investigates the diagnostic accuracy of IgG anti-deamidated gliadin peptide (DGP), IgA and IgG anti-tissue transglutaminase (tTG), IgG anti-gliadin (AGA), and IgG anti-endomysial antibodies (EMA) in diagnosing celiac disease (CD), particularly in patients with IgA deficiency. Methods: A case-control study was conducted with 118 participants, including 68 newly diagnosed CD patients and 50 healthy controls. Serum samples were collected and analyzed using the Sandwich-ELISA technique. Statistical analysis included chi-square tests, ANOVA, logistic regression, and Spearman correlation, using SPSS v26. Results: Antibody concentrations were significantly elevated in CD patients compared to controls (p = 0.0001). Median levels of anti-gliadin IgG, EMA IgG, DGP IgG, tTG IgA, and tTG IgG in patients were 40.8 ng/ml, 345.5 pg/ml, 11.5 nml/l, 2.85 ng/ml, and 95.5 ng/ml, respectively. Significant inverse correlations were observed between gliadin-IgG and EMA (-30.2%, p = 0.012), tTG IgA (-23.8%, p = 0.0001), and tTG IgG (-39.7%, p = 0.001). EMA demonstrated direct correlations with DPG (49%, p = 0.0001), tTG IgA (36.4%, p = 0.002), and tTG IgG (34.1%, p = 0.004). Novelty: This study highlights the diagnostic utility of IgG anti-DGP as a reliable marker in IgA-deficient populations and underscores the correlations among antibody markers, providing insights into their synergistic roles in CD diagnosis.

Frequency of microscopic colitis in patients presenting with chronic diarrhea.

Objective: To evaluate frequency of microscopic colitis in patients presenting with chronic diarrhea at a tertiary care hospital in Karachi, Pakistan. Study Design: Descriptive Cross-sectional study. Setting: Department of Gastroenterology, Liaquat National Hospital, Karachi, Pakistan. Period: January, 2022 to June, 2022. Material & Methods: Patients presenting in out-patient department of age >18 years of any gender with history of diarrhea >1 month, normal thyroid tests, negative serology for Celiac disease (Anti TTG IgA and IgG), and normal colonoscopy findings including terminal ileum were enrolled in the study after written informed consent. MC diagnosis was established using clinical diarrhea history and colonic biopsy findings. Results: Total 130 patients were analyzed with median age of 38 (IQR= 28-55) years. Nearly half were females (n=67, 51.5%). All patients had normal colonoscopy findings. Out of 130 patients, microscopic colitis was seen among 7(5.4%) cases out of which 5(3.8%) had lymphocytic colitis and 2(1.5%) had collagenous colitis. Patients with and without MC shared the same characteristics. Conclusion: A lower microscopic colitis frequency was found in the studied sample. Lymphocytic microscopic colitis is predominant than collagenous microscopic colitis.

Prevalence of Coagulopathy in Patients with Celiac Disease: A Single-Center Retrospective Case-Control Study

Introduction: Despite being one of the most frequent chronic digestive diseases worldwide, with a prevalence of 1%, celiac disease (CD) remains severely underdiagnosed. Among the instruments used to improve its diagnostic rate, hematologic parameters have been proposed as screening tests to select patients with an increased probability of having CD. Assessment of coagulation is included in routine check-ups, and CD has been reported to be associated with coagulopathy. We aimed to assess if subtle changes in coagulation tests could be used in clinical practice to prompt testing for CD. Methods: We retrospectively recruited all patients with clinical suspicion for CD during a study period of 7 years (between 2015 and 2022), who were tested using IgA tissue transglutaminase (tTG) serology and serum total IgA (IgG tTG in case of IgA deficiency) and who underwent upper gastrointestinal endoscopy with multiple biopsy sampling of the duodenal bulb and distal duodenum. We stratified patients into three groups: newly diagnosed CD, gluten-free diet-treated CD, and non-CD controls. Results: Altogether, there were 133 CD patients (71 newly diagnosed, 62 GFD-treated) and 57 non-CD controls. Mean age and gender distribution were similar among the three groups: 43.3 years for newly diagnosed CD, 41.6 years for non-CD controls, and 44 years for GFD-treated CD patients, with a male gender distribution of 21.1%, 28%, and 24.1%, respectively. Among the included newly diagnosed CD patients, 14% had a prolonged INR. The mean INR was slightly higher in newly diagnosed CD patients, compared to GFD-treated CD patients and non-CD controls: 1.12 ± 0.30, 1.02 ± 0.83, and 1.00 ± 0.08, respectively (p = 0.009). Consequently, prothrombin activity was slightly lower in newly diagnosed CD patients, compared to GFD-treated CD and non-CD controls: 94.9 ± 19.3%, 102.3 ± 12.8%, and 101.9 ± 15.15, respectively. Interestingly, after GFD, the mean INR and prothrombin activity of CD individuals reached a value similar to that of non-CD controls. Conclusions: Subtle changes in INR, defined as a value within the normal range, but closer to the upper limit, could be an indicator of probability for CD.

THU436 Small Intestinal Bacterial Overgrowth Causing Osteoporosis In An Adult Male

Abstract Disclosure: S. Aziz: None. S.A. Patrick: None. V. Mupparaju: None. S. Kode: None. Background: Small intestinal bacterial overgrowth (SIBO) is a disease caused by intestinal dysbacteriosis which can lead to nutrients malabsorption and chronic metabolic acidosis which affect bones health and cause osteoporosis. Clinical Case: A 45-year-old man with medical issues of GERD presents to the endocrinology clinic in 02/2022 for evaluation of incidental finding of T5 vertebral fracture noted in the chest x-ray done for evaluation of chest tightness. During the clinic visit the patient reported chronic bloating and gassiness. Denied symptoms suggestive of eating disorders, chronic fatigue, decreased libido, recurrent fractures, elastic skin, hypermobile joints or joint dislocation, and steroid use. Patient is married and has two biological children. He drinks alcohol socially and denied tobacco use. Patient was taking cholecalciferol 1000 IU daily at home. His weight is 64 kg with a BMI of 21 kg/m2. Physical examination did not reveal any abnormality. Bone mineral density showed the worst Z-score of -2.3 in his spine. Workup for osteoporosis included 24-hour urine calcium, CBC, CMP (including serum calcium, phosphorus, electrolytes, ALP, and creatinine), PTH, TSH, free plasma cortisol, ACTH, morning total testosterone, 25-hydroxyvitamin D level, SPEP, UPEP, celiac disease screening tests (tissue transglutaminase IgA and tTG IgG), IGF-1 and HbA1c were all within normal limits. The patient was started on alendronate 70 mg once weekly and was referred to a local gastroenterologist for further evaluation of his GI symptoms; he subsequently was diagnosed with SIBO which is the most likely cause for his osteoporosis. Conclusion: SIBO is a disease caused by intestinal dysbacteriosis, which is caused by replacement of physiologic bacteria by pathogenic bacteria from the large intestine leading to maldigestion and malabsorption of nutrients including fat, carbohydrates and protein leading to vitamins deficiencies and metabolic acidosis. Due to impaired absorption of nutrients it can cause systemic complications including osteoporosis. Fat malabsorption can lead to deficiencies of fat-soluble vitamins A, D, K and E. SIBO can also result in protein-losing enteropathy. The state of chronic metabolic acidosis caused by SIBO increases alkali mobilization from the bone and induces dissolution of the bone thus promotes the development of osteoporosis. Gastrointestinal diseases including SIBO should be considered in cases of osteoporosis of unknown origin. Presentation: Thursday, June 15, 2023

B-055 Comparison of Sensitivity Between Tissue Anti-Transglutaminase and Anti-Endomysium IgA and IgG in Serological Screening for Celiac Disease in a Large Clinical Laboratory in Brazil

Abstract Background Celiac Disease (CD) is a genetic and autoimmune disorder characterized by permanent intolerance to gluten found in foods, resulting in small intestine injury in children and adults. Anti-tissue transglutaminase (anti-tTG) and anti-endomysium (anti-EM) antibodies are important serological markers of this disease. The aim was to analyze the analytical sensitivity of these markers in a large-scale Clinical Laboratory routine. Methods We employed a pure sample and a series of dilutions in the analysis of the functional sensitivity of each marker (anti-tTG IgA/IgG and anti-EM IgA/IgG) and a database survey of a large Clinical Laboratory in Sao Paulo/Brazil, from January to December 2021, analyzing 60 000 samples with concomitant results of anti-tTG IGA and anti-EM IgA and 7075 samples with results of anti-tTG IgG and anti-EM IgG, from patients with no defined clinic condition. The anti-tTG tests were performed by fluorescence enzyme immunoassay (FEIA) and the anti-EM tests by indirect immunofluorescence (IFI), with an initial dilution of 1:10, following the manufacturer's recommendations. Results The determination of functional sensitivity by checking the maximum dilution of antibody detection showed higher sensitivity of the anti-tTG IgA and IgG test (dilution factor 0.3 for both) compared to the anti-EM IgA and IgG (dilution factor 0.7 for both). Of the 60 000 samples analyzed for IgA markers, 59 083 (98.5%) were negative for both tests. Of the remaining 917 samples (1.5%), 609 (66.4%) were positive for both anti-tTG IgA and anti-EM IgA, 308 (33.6%) were positive only for anti-tTG IgA, and we did not observe any sample anti-tTG IgA negative with anti-EM IgA positive. Of the 7075 samples analyzed for IgG markers, 7032 (99.4%) were negative for both tests. Of the remaining 43 samples (0.6%), 18 (41.9%) were positive for anti-tTG IgG and anti-EM IgG, 14 (32.6%) were positive only for anti-tTG IgG, and 1 (2.3%) were positive only for anti-EM IgG. Conclusion The study showed greater sensitivity of anti-tTG compared to anti-EM for both IgA and IgG, in agreement with the literature data. The anti-tTG IgA test, in individuals without immunoglobulin A (IgA) deficiency, is recommended as the initial test in suspicion of celiac disease by current scientific guidelines on celiac disease. Based on our findings and literature data, in individuals with IgA deficiency, we suggest a screening using two automated IgG markers, tTG IgG and deamidated gliadin IgG (DG IgG). In addition to the lower sensitivity of anti-EM, indirect immunofluorescence (IFI), compared to the fully automated FEIA method, is a more subjective, observer-dependent, and labor-intensive methodology to be used as screening in large-scale Clinical Laboratory routines.

Variability in Celiac Serology Testing by Provider Type: A Single-Center Experience.

We analyzed celiac serologies ordered in 2018 by provider type (pediatric gastrointestinal (GI) specialists, primary care providers (PCPs), and nonpediatric GI specialists), and identified causes for variability and nonadherence. The antitissue transglutaminase antibody (tTG) IgA was ordered (n = 2504) most frequently by gastroenterologists (43%), endocrinologists (22%), and other (35%). Total IgA was ordered with tTG IgA for screening purposes in 81% of overall cases, but endocrinologists ordered it only 49% of the time. The tTG IgG was ordered infrequently (1.9%) compared with tTG IgA. Antideaminated gliadin peptide (DGP) IgA/IgG levels were also infrequently ordered (5.4%) compared with tTG IgA. The antiendomysial antibody was ordered sparingly (0.9%) compared with tTG IgA, but appropriately by providers with expertise in CD, similar to ordering for celiac genetics (0.8%). Of the celiac genetic tests, 15% were ordered in error. The positivity rate of the tTG IgA ordered by PCPs was 4.4%. The tTG IgA was appropriately ordered by all types of providers. Endocrinologists inconsistently ordered total IgA levels with screening labs. DGP IgA/IgG tests were not commonly ordered but were inappropriately ordered by one provider. The low number of ordered antiendomysial antibody and celiac genetic tests suggests under-utilization of the nonbiopsy approach. The positive yield of tTG IgA ordered by PCPs was higher compared with previous studies.

Assessment of diagnostic value of HLA-DQ2/DQ8 typing and anti-tissue transglutaminase antibodies as an alternative to duodenal biopsy in pediatric celiac disease

Introduction/Objective. The objective of the paper is to assess the applicability of serum anti-tissue transglutaminase (tTG) antibodies IgA and IgG concentration and HLA-DQ2/DQ8 typing as a non-invasive alternative to duodenal biopsy in diagnosing celiac disease (CD) in pediatric population. Methods. A prospective cohort study included a total of 179 pediatric patients aged 1?18 years. Determination of tTG IgA and tTG IgG antibodies and human leukocyte antigen (HLA) DQ2/DQ8 typing was performed for all patients. Histology of duodenal biopsies was interpreted by the modified Marsh scoring system. Results. The diagnosis of CD was confirmed in 101 (56%) patients of the studied population. In cases of CD, HLA-DQ2/DQ8 was positive in 100 patients (99%). The tTG IgA antibodies in concentration higher than 100 U/ml were detected in 77 (76.2%) of the CD patients and in significantly smaller number for tTG IgG [29 (28.7%)] (p < 0.001). Statistically highly significant association of duodenal lesions Marsh grade 3 with concentration of tTG IgA 10-fold higher than the upper level of normal (ULN) was established (p < 0.001) Conclusion. Concentration of tTG IgA 10-fold higher than ULN is significantly positively correlated with Marsh grade 3 histopathology findings. Specific antibodies determination in combination with HLA-DQ2/ DQ8 typing proves to be sufficient for a diagnosis of CD, supporting the fact that duodenal biopsy may be avoided in a significant majority of patients ? 75%.

Frequency of Celiac Disease in Microcytic Anemia Patients of Nowshera

Background: Celiac disease a chronic gastrointestinal disorder is caused by an immune response to the gluten. Numerous studies have been conducted worldwide on the relationship between anemia and celiac disease. Objective: To find out the frequency of celiac disease in microcytic anemia patients of Nowshera Methodology: The current study was cross sectional carried out at the Gastroenterology department, Qazi Hussain Ahmad Medical Complex, Nowshera from October 2021 to October 2022. For serological diagnosis of the celiac disease, all the patients were tested for IgA and IgG tTG (anti-tissue transglutaminase). OesophagoGastroDuodenoscopy (OGD) was done for all the patients with raised level of IgA and IgG tTG (anti-tissue transglutaminase). All the analysis of collected data was done by employing IBM SPSS version 24. Results: In this study a total of 300 patients with microcytic anemia were enrolled. There were 165 (55%) female participants while 135 (45%) patients were male. IgA and IgG tTG (anti-tissue transglutaminase) levels were raised in 15 (5%) patients amongst 300 patients with microcytic anemia. In duodenal biopsy of 15 patients with celiac disease, Marsh I was observed in 4 (33.33%) patients, Marsh II in 5 (41.67%) patients, Marsh III in 3 (25%) patients, while 3 (20%) cases showed normal histo-pathological findings. Thus the overall frequency of celiac disease amongst microcytic anemia patients was 15 (5%). Conclusion: Our study concludes that celiac disease is more prevalent amongst the patients with microcytic anemia. The microcytic anemia can be considered as additional gastrointestinal manifestation of the celiac disease. Keywords: Frequency; Celiac disease; Microcytic anemia

Anti-tissue Transglutaminase Enzyme-Linked Immunosorbent Assay for Screening of Celiac Disease in Moroccan Pediatric Patients

Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten which induces an enteropathy with atrophy of intestinal villi. No prevalence information was available for CD in Moroccan children because the diagnosis is based on multiple invasive duodenal biopsies. To simplify CD diagnosis, the objective of this work was to develop an Enzyme-linked Immunosorbent Assay (ELISA) for IgA and IgG tissue transglutaminase (tTG) antibodies detection suitable for Moroccan children. The concentration of the coated antigen and serum dilutions were optimized for the development of IgA anti- tTG and IgG anti-tTG ELISA detection in serum. The cut-off was calculated and the developed ELISAs were used for detecting IgA and IgG-tTG antibodies in 97 serum samples from 97 children aged 1 to 13 years, with variable clinical characteristics. After adjusting optimal working conditions of ELISA, the cut-offs were 0.04 and 0.156 AU for detecting anti-tTG and IgA anti-tTG IgG respectively. The use of IgG anti-tTG as CD marker (100 % of sensitivity) was better than the use of IgA anti-tTG in ELISA tests (90.3% sensitivity). In addition, the ELISA test shows a clear correlation between the IgG tTG antibodies titer and the degree of duodenal damage, estimated by the Marsh stages classification in patients with confirmed CD. Our results suggest that the assessment of the adapted IgG anti-tTG ELISA test can be used for CD in initial screening in Moroccan children after validation with a larger number of samples with CD for confirmation.

Clinical Characteristics and Outcomes of Patients with Positive Celiac Serology and Cancer Therapy Exposure.

Objectives: The prevalence of celiac disease (CD) among cancer patients is unknown, yet new cases of CD occur after cancer therapy exposure. The aim of this study was to describe the clinical course and endoscopic features of patients with positive celiac serology (PCS) post-cancer therapy exposure (PCTE) as compared to those with no cancer therapy exposure (NCTE).Methods: A retrospective study of adult patients with PCS at MD Anderson Cancer Center between March 2009 and May 2020. Patients with positive tTG IgA, tTG IgG, and/or EMA IgA were categorized into cases with NCTE and PCTE. Clinical course, endoscopic and histologic features, and treatments were compared between the two groups.Results: Of the 4,345 patients screened for celiac serology, 21 (0.5%) met inclusion criteria. 12 were PCTE, with a median time of 258 days (173-930 days) from initiation of the last cancer therapy. Those PCTE had a higher rate of diarrhea (75% vs 22%, p = 0.030), malnutrition and death. A gluten-free diet was initiated in 82% PCTE vs 89% NCTE, with the majority experiencing symptom resolution. There were no significant differences in endoscopic and histologic features. 17 patients met criteria for CD diagnosis.Conclusions: Our findings suggest that CD may be under-diagnosed in cancer patients. Patients with PCS after cancer therapy may present with diarrhea, nutritional deficiencies, and malnutrition, yet a gluten-free diet may be efficacious in treatment management. Therefore, CD should be considered when treating cancer patients. Given the relative proximity of PCS to cancer therapy exposure, future studies should investigate the association of cancer and cancer therapy with the development of CD.

Celiac Disease in Short Stature Pediatric Population Presenting to Endocrinology Clinics: A Cross-Sectional Study from a Tertiary Care Hospital in Karachi

Background: Among many reasons, short stature is one of them for referring children to paediatric endocrinology. The most frequent extra-intestinal symptom of celiac disease is short stature (SS). A very high probability of celiac disease is reported among children with SS for non-endocrinological reasons. Objective: To ascertain the frequency of celiac diseases among short-stature children presenting in endocrinology clinics in a tertiary care hospital. Methods: This descriptive cross-sectional study was performed in pediatric endocrinology clinics at the National Institute of Child Health for a six-month duration from February 2022 to July 2022. All short-stature children of any gender and age from 2 to 12 years were included in the study. Short stature was defined as height for age < -2 standard deviation for the corresponding age and gender. Serological investigation including Immunoglobin A (IgA), anti-tissue-transglutaminase antibodies (TTG IgA) and TTG IgG test was done by ELISA (enzyme-linked immunosorbent assay) method for all of the patients recruited into the study. Results: A total of 149 children with short stature were studied. The mean age of children was 10.2 ± 3.1 years. The majority of patients were males 53.7%. Average height and height for age z-score were 104.8 ± 8.9 cm and -5.1 ± 1.9 respectively. Out of 149 children, only 6.7% had positive serology for celiac diseases. None of the patients' factors was significantly different among patients with and without celiac disease. Conclusion: The current investigation discovered that patients with low stature had a substantial frequency of celiac disease. It was discovered that none of the patients' demographics were linked to celiac disease. For prompt diagnosis and treatment of celiac disease, people with short height should undergo screening.

GGLUTEN-SENSITIVE ENTEROPATHY - NEW VIEW ON PROBLEM

Gluten sensitive enteropathy-celiac disease is an immune-mediated disorder caused by permanent sensitivity to gluten in genetically susceptible individuals. Epidemiologic studies of last years suggest that it is common and may occur in 0,5-1% of the general population. The bowel inflammatory and immunologic response results in atrophy and damage in the small bowel and secondary malabsorbtion. The mode of presentation can be quite variable. Celiac disease is generally defined as chronic diarrea and failure to thrive in infants and toddlers, diarrhea is still the most common symptom, but disease may occure in different age groups and with exstraintestinal, sometimes monosymptomic clinic. Clinical forms of celiac disease are: classic, atypical, silent, latent and potential. Definitive diagnose of Celiac disease requires serrologic screening, small intestinal biopsy and effectiveness of elimination diet. Anti-tissue transglutaminase antybody test (TTG IgA and TTG IgG) is highly sensitive, specific and less expensive, thus is recommended for general practice. None of serologic tests are 100% reliable. Definitive diagnosis requires characteristic histologic changes in intestine mucus. Tissue for investigation may be taken from duodenum during gastro endoscopy. Diagnosing only by results of gluten-free diet is not correct. The only treatment for celiac disease is lifelong exclusion of gluten. Early diagnosis and strict dietary restrictions appear to be the only possibility of prevention risk for failure to thrive, delay of sexual maturity, autoimmune disorders, adenocarcinoma of gastrointestinal tract and lymphoma.

Nonresponsive Celiac Disease Treated with a Unique Functional Medical Approach

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

İç Anadolu Bölgesinde Çölyak Hastalığının İdiyopatik İnfertilite ile İlişkisi

Aim: Celiac Disease (CD) is an inflammatory autoimmune disease that occurs in the small intestine of genetically predisposed individuals after gluten intake. CD leads to several gynecological and obstetrical problems. We aimed to investigate the prevalence of CD in patients with the diagnosis of idiopathic infertility in Central Anatolia. Patients and Methods: The study included 30 female patients who had the diagnosis of idiopathic infertility in the Erciyes UniversityFaculty of Medicine, gynecology and obstetrics clinic and 33 healthy women with at least one healthy pregnancy. The levels of AGA IGG/IGM, EMA, tTG, and IgG/IgM antibodies were measured in all patients and the study group. Upper gastrointestinal endoscopy and duodenal biopsy were performed for the individuals with a positive test result. Results: There was no significant difference in the presence of anemia, age, and body mass index between the groups. While AGA IGA was positive in four patients and AGA IGG was only positive in one patient in the patient group, AGA IGA was positive in three patients in the control group. In the control group, only one patient had a positive (EMA) test result; however, there was no positive result in any of the patients in the study group. TTG IgA antibodies were negative in both groups. Two patients had positive test in terms of TTG IgG in the control group. There was no statistically significant difference in terms of serological tests in both groups. Conclusion: The prevalence of CD in idiopathic infertile patients was similar to the control group. Further studies are needed to evaluate this relationship in this cohort.

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 & 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.

Juvenil İdiopatik Artrit Hastalarında Çölyak Hastalığı ve Çölyak Dışı Gluten Duyarlılığı Taraması

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children characterized by autoimmune etiology. In previous studies, increase In the Incidence of celiac disease (CD) was reported in patients diagnosed with JIA. In this study, the presence of CD and non-celiac gluten sensitivity (NCGS) in patients diagnosed with JIA were investigated. METHODS: Sixty-one (57.3%) JIA patients admitted to the pediatric rheumatology outpatient clinic between January 2020 and April 2020 were included in this cross-sectional study. All patients were evaluated with clinical and laboratory findings in terms of CD and NCGS. Total immunoglobulin (Ig)-A, tissue transglutaminase antibody (tTG) IgA and IgG, anti-endomysium-antibody (EMA) IgA and IgG and anti-gliadin-antibody (AGA) IgA and IgG levels were measured in all patients. RESULTS: Sixty-one JIA patients Including 35 girls, were enrolled in the study. The mean age of the patients was 11.4±4.6 years, the mean age at diagnosis was 10.2±3.4 years. Patients were diagnosed with oligoarticular JIA (n=33), enthesitis-related arthritis (n=18), polyarticular JIA (n=8), and psoriatic arthritis (n=2). All patients were using disease-modifying antirheumatic drugs during the study. Thirty-five patients were receiving biological therapy, concomitantly. The patients (n=2) had abdominal pain, indigestion (n=2), and constipation (n=2). None of the patients had growth retardation. EMA IgA and IgG, tTG IgA and IgG, AGA IgA and IgG tests were negative in all patients. DISCUSSION AND CONCLUSION: CD and NCGS were not detected in our JIA patients. Multicenter studies may guide the clinicians about the circumstances to perform CD and NCGS screening in JIA patients.

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk

To investigate if the amount of gluten intake during the first 5 years of life in genetically predisposed children is associated with increased risk of celiac disease autoimmunity and celiac disease.This prospective observational birth cohort study, The Environmental Determinants of Diabetes in the Young (TEDDY), followed children from birth up to 15 years of age at 6 clinical research centers in Finland, Sweden, Germany, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Data on gluten intake were available in 6605 children (49% female) and this was the group included in the analysis. Median follow-up was 9.0 years (range, 1.0–13.0 years).Serum tissue transglutaminase (tTG) autoantibodies were measured annually in 6757 children from the age of 2 years. Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and then biannually until 5 years old. Composite foods and recipes were broken down to ingredients. Absolute gluten intake (grams/day) was calculated.The primary outcome was celiac disease autoimmunity, defined as positive tTG autoantibodies found in 2 consecutive serum samples. Radiobinding assays were used to measure autoantibodies. In the US centers, IgA–tTG autoantibodies were measured. In the European centers, both IgA and IgG–tTG autoantibodies were measured. Diagnosis of celiac disease was confirmed by intestinal biopsy (Marsh score ≥2) or if a biopsy was not done, by persistently elevated tTG autoantibody levels (average of 2 yearly samples ≥ 100 U). Decision to perform endoscopy and biopsy was not determined by study protocol.1216 (18%) children developed celiac disease autoimmunity, and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at 2 to 3 years of age. Children homozygous for HLA DR3-DQ2 were at the highest risk of celiac disease autoimmunity and celiac disease. Swedish residence, female sex, and family history of celiac disease were also associated with increased risk for both outcomes. The authors found that higher gluten intake during the first 5 years after birth was associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.30 [95% CI, 1.22–1.38]; absolute risk of 28.1% by the age of 3 years if a reference amount of gluten was consumed; absolute risk was 34.2% if the gluten amount consumed was 1-g/d higher than the reference amount. Similarly, the authors found that higher gluten intake during the first 5 years after birth was associated with an increased risk of celiac disease (hazard ratio, 1.50 [95% CI, 1.35–1.66]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if the gluten amount consumed was 1-g/d higher than the reference amount, 27.9%. A post hoc analysis that focused on dietary gluten intake at the age of 2 years (just prior to the peak of celiac disease autoimmunity or celiac disease) found that daily gluten consumption of as little as 2 g (equivalent to 1 slice of bread) was associated with an increased risk of developing celiac disease autoimmunity or celiac disease; that risk was further increased for each gram of gluten ingested beyond this threshold.Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.In an accompanying editorial, it was pointed out that the amount of gluten ingested during the first 5 years after birth cannot completely explain the increased prevalence of celiac disease. Previous work examining the relationship between HLA genetics, gluten consumption, and celiac disease prevalence found no significant relationship between the amount of gluten ingested and the prevalence of celiac disease. As well, the prevalence of celiac disease in Finland is higher (1%–2.5%) than in Italy (0.7%–1.1%), yet infant wheat consumption in Italy is much higher than in Finland. Further investigation is needed, but pediatricians could consider counseling families of known genetic predisposition for celiac disease or type 1 diabetes to delay or diminish gluten ingestion in infants.

S2531 A Rare Cause of Cholestasis: Secondary Sclerosing Cholangitis in a Critically Ill Patient

INTRODUCTION: Secondary sclerosing cholangitis in critically ill patient (SSC-CIP) is a newly diagnosed entity of severe biliary disease which can rapidly progress to liver cirrhosis. The mechanism leading to this form of cholangitis with stricture formation and complete obliteration of bile ducts is unknown (1). CASE DESCRIPTION/METHODS: 47 year old woman with history of roux en y gastric bypass was admitted for status epilepticus, pneumonia and shock requiring vasopressors and ventilator support for over a month in ICU. Patient’s LFTs at discharge were normal. Patient was readmitted few weeks later with a seizure and found to have abnormal LFTs (ALP 2500, GGT 4000, direct bilirubin 3.2, ALT 80, and AST 75, lipase 80) which persisted over the course of next ten months. The negative work up included HAV, HBV, HCV, HIV, ANA, AMA, ASMA, Immunoglobulins, Anti LKM, ANCA, Anti SP 100, Anti GP 210, ceruloplasmin, alpha 1 anti-trypsin, TTG IgG, TSH, AFP, CA19-9 and leukemia/lymphoma markers. Her ultrasound and CT scan was unremarkable. Patient was unable to get a MRCP due to a vagal nerve stimulator and ERCP was not done due to difficult anatomy. She underwent a IR guided cholangiogram; subtle stricturing and mild dilation of left intrahepatic ducts seen, followed by a liver biopsy. Biopsy showed large bile duct obstruction with secondary sclerosing cholangitis due to ischemic cholangiopathy with advanced biliary fibrosis. Patient was started on ursodiol with improvement of LFTs however she got readmitted few days later with hemorrhagic shock due to delayed bleed from the liver biopsy site with sepsis and multiorgan failure resulting in death. DISCUSSION: SSC-CIP can be caused by events such as prolonged hypotension and respiratory insufficiency that lead to severe irreversible injury of ducts (2). The trigger event of ischemic cholangoipathy in our patient was likely her initial critical illness (hypotension and respiratory failure) resulting in cholestasis. This variant SSC-CIP is a relatively new disease that is an under recognized cause of cholestasis and should be suspected as a differential in patients with new cholestasis after a critical illness.

Frequency of celiac disease in patients with vitiligo

Background: Celiac disease (CD) is an autoimmune and inflammatory disease that occurs in the small intestine as a result of gluten intake in individuals. Vitiligo, in which autoimmune factors play an essential role, is associated with depigmentation due to the loss of epidermal melanocytes. Many autoimmune diseases are known to be associated with vitiligo. This study aims to determine the frequency of CD in vitiligo cases.Methods: Out of 61 vitiligo patients, 32 (52.4%) are women, and 29 (47.6%) are men; of the 119 healthy volunteers, 58 (48.7%) are women, and 61 (51.3%) are men. Serum levels of tissue transglutaminase (tTG) IgA and tTG IgG antibodies were measured in all participants. If at least one of these two antibodies are positive, mucosal biopsies were taken from the second section of the duodenum by endoscopy.Results: There is no significant difference between the study group and the control group in terms of age and body mass index (BMI) (p=0.16, p=0.80, respectively). tTG IgA and tTG IgG were positive in one patient in each group. In both patients, the results of the duodenal biopsy were histopathological compatible with CD. There was no difference between the vitiligo group and the control group in terms of CD frequency (p=0.56).Conclusion: The frequency of CD in vitiligo patients is similar to the control group. However, it should be kept in mind that the frequency of CD in patients with vitiligo may be higher than the rates assumed incidental, and necessary research should be carried out for early diagnosis in such patients.

Autoimmune Markers in Children with Chronic Immune Thrombocytopenia

Introduction: Chronic immune thrombocytopenia (ITP) is defined as isolated thrombocytopenia lasting longer than 12 months. Rheumatologic diseases, immunodeficiencies and thyroid diseases may coexist with chronic ITP due to possible immune dysregulation.Aim: To evaluate the accompanying autoimmune diseases in children with chronic ITP.Materials-Methods: A total of 154 children with chronic ITP (F /M: 1) diagnosed between 1995 and 2018 were included. Patients were evaluated with immunoglobulin levels, ANA, anti dsDNA, C3, C4, anti TPO, anti TG, T4, TSH, tissue transglutaminase IgA and Ig G.Results: Of the 154 patients, 79 were female (51.3%) and 75 were male (48.7%). Mean age of the patients was 13.6 ± 5.8 years, mean age of diagnosis was 7 years ± 4. None of the patients had severe infections requiring hospitalisation. None of the patients had symptoms or findings of an autoimmune disorder. Of 154, two had low IgA levels (<7 mg / dL) and they were diagnosed as IgA deficiency. IgM and IgG levels were normal in all. C3 level was low in four patients (3%) and C4 level was low in one patient (0.7%). ANA was positive in 16 (12%) of the patients and anti-dsDNA was positive in four patients (0,3%). In three patients, Anti-dsDNA positivity was accompanied with ANA positivity and in one patient, C3 was low. These patients were followed up by pediatric rheumatology clinic. Twenty two patients had elevated anti TPO (15.5%) and 18 patients had elevated anti TG (12.7%) levels. Majority of patients with high thyroid autoantibodies were female (67.5%). Out of 129 patients evaluated by thyroid tests including fT4, TSH, AntiTPO and AntiTG, 29 (% 22,4) were diagnosed as Hashimoto thyroiditis. Thyroid hormone replacement was started in one patient . Of 93 patients evaluated with anti-tissue transglutaminases, 7 were found to have at least one positive TTG IgA or IgG. Two of these patients underwent endoscopy, but no evidence of celiac disease was found. In total, the number of patients with at least onepositive autoimmune marker was 54 (35%).Discussion and Conclusion: Chronic ITP is known to accompany autoimmune diseases. Autoimmune diseases in patients with ITP may occur at any time in 10 years of diagnosis. Further studies for the detection of subclinical autoimmune conditions should be performed with a profit- loss account. Antibodies may be positive even when there is no clinical findings of the diseases. Further follow-up is needed to understand the clinical significance of autoimmune markers in chronic ITP. DisclosuresNo relevant conflicts of interest to declare.