tTG Antibodies Research Articles

Prevalence of Autoantibodies in patients with Hereditary Alpha Tryptasemia.

Hereditary alpha-tryptasemia (HT) is associated with postural orthostatic tachycardic syndrome (POTS), hypermobile Ehlers Danlos Syndrome (hEDS), and mast cell activation syndrome (MCAS). While POTS, hEDS and MCAS have all demonstrated increased prevalence of autoimmunity, this has not been investigated in HT populations. Our objective was to describe the prevalence of autoantibodies in individuals with HT. We retrospectively studied a cohort of patients with positive genotyping for HT at a tertiary care allergy clinic. Demographic data including previous autoimmune history and autoantibody serologies were extracted on chart review. A literature search was conducted to determine the prevalence of specific autoimmune and autoantibody prevalences in the general population. We compared the proportions of autoantibody positivity and established autoimmune diseases in our cohort of HT individuals against those in general populations. We identified 101 patients with HT. Median age was 43 years (range 15-75) and most were female (87/101; 86.1%). Prevalence of self-reported drug hypersensitivity was 52/101 (52.5%) patients. The proportion of individuals with HT with positive tTG antibody (3/61, 4.9%) was significantly higher than that reported in the general population (133/16667, 0.8%) (p<0.001). The prevalence of SLE (1/101, 1%) and celiac disease (5/101, 5%) in our cohort were found to be significantly higher than the prevalence in the general population [194/96996, 0.2% (p=0.035) and 26/2845, 0.9% (p<0.001), respectively]. Patients with HT have increased prevalence of celiac disease, SLE and positive anti-tTG serology as well as self-reported drug hypersensitivity, relative to general populations.

Anti-tissue transglutaminase antibody correlation with severity of villous abnormalities in celiac disease: A Systematic Review and Meta-analysis

Abstract Introduction/Objective Celiac disease (CD) is a long-term autoimmune disorder that affects individuals genetically predisposed to gluten intolerance. Biomarkers, particularly anti-tissue transglutaminase antibody (anti-tTG ab), are crucial in indicating disease states and have potential as non-invasive substitutes for mucosal biopsies in assessing the severity of intestinal damage. This study aims to systematically review and analyze the correlation between anti- tTG antibody levels and the severity of villous abnormalities in patients with celiac disease to evaluate the potential of anti-tTG as a non-invasive diagnostic tool. Methods/Case Report Following PRISMA guidelines, a comprehensive literature search selected 15 studies focusing on the correlation between anti-tTG antibodies and villous atrophy. Systematic data extraction and quality assessments were performed, followed by statistical analyses to determine the strength and consistency of associations. Results (if a Case Study enter NA) Analysis of data from four studies on anti-tTG antibody positivity revealed a nearly significant pooled effect size (p = 0.06) with considerable heterogeneity (I^2 = 97%, p &amp;lt; 0.00001). Additionally, data from five studies using the MARSH classification of histological damage, aggregated using a random-effects model, showed overall statistical significance (Z = 3.36, p = 0.0008). Conclusion Anti-tTG antibodies serve as a reliable indicator of villous damage in CD, supporting their dual utility in diagnosis and monitoring. High anti-tTG antibody titers could potentially eliminate the need for invasive biopsy procedures in certain patient subsets, underscoring the promise of more refined and non-invasive diagnostic approaches, although further research is needed to address the implications of high heterogeneity observed in the studies.

B-052 Celiac Disease Risk Assessment of HLA-DQ Typing in IgA Deficient Patients

Abstract Background Celiac disease (CeD) is a chronic autoimmune disorder triggered by the ingestion of gluten in persons with the genetic risk factors human leukocyte antigens (HLA)-DQ2 and DQ8. Diagnostic evaluation of patients with suspected CeD often includes serology tests for tissue transglutaminase (tTG) antibodies. While the presence of HLA-DQ2 or DQ8 is required for the initiation and development of CeD, the genetic risk associated with the various alleles is not equivalent. Previous studies in patients with normal total IgA demonstrated the risk gradients of various HLA-DQ2 and DQ8 heterodimers in CeD. However, the impact of both gene variants in IgA deficient patients has not been investigated. In this study, HLA-DQ2 and HLA-DQ8 as risk factors for tTG-IgG positivity in IgA deficient patients were evaluated. Methods Retrospective data was collected from a cohort of individuals (n=3,515) with IgA concentrations below the age-dependent reference interval with suspicion for CeD who were tested for HLA-DQ genotyping and tTG-IgG (reference interval &amp;lt; 6 U/mL) at Mayo Clinic Laboratories. Total IgA was measured using quantitative nephelometry (Siemens BN™ II System); HLA typing was performed using the reverse SSO DNA typing assay (LABType SSO kits). tTG-IgG was determined by enzyme-linked immunosorbent assay (QUANTA Lite R h-tTG, Werfen Diagnostics) on the Dynex Agility System. The prevalence and frequency distribution of HLA-DQ2 and DQ8 haplotypes were determined and the odds ratio (OR) was calculated to evaluate the risk gradient for tTG-IgG positivity based on different HLA-DQ variants. Results Among IgA deficient patients, 58% (n=2,041) expressed HLA-DQ2 or DQ8 haplotypes. Relative to patients without permissive alleles, patients homozygous for HLA-DQ2.5 exhibited a significantly increased risk for tTG-IgG positivity (OR = 10.98, 95% CI: 6.56-18.18, p &amp;lt; 0.001) while those homozygous for HLA-DQ2.2 and DQ8 did not (DQ2.2/DQ2.2_OR = 0.72, 95% CI: 0.04-3.44, p = 0.75; DQ8/DQ8_OR = 0.96, 95% CI: 0.05-4.64, p = 0.97). Patients heterozygous for HLA-DQ2.5 (DQ2.5/x) displayed a lower odds ratio relative to homozygous patients (OR = 3.31, 95% CI: 2.29-4.82, p &amp;lt; 0.001); however, the risk for tTG-IgG positivity increased in the presence of HLA-DQ2.2 (DQ2.5/DQ2.2_OR = 7.59, 95% CI: 4.48-12.65, p &amp;lt; 0.001) or HLA-DQ8 (DQ2.5/DQ8_OR = 6.26, 95% CI: 3.55-10.73, p &amp;lt; 0.001) alleles. Conversely, in the absence of HLA-DQ2.5, HLA-DQ2.2 heterozygotes (DQ2.2/x_OR = 2.80, 95% CI: 1.77-4.39, p &amp;lt; 0.001) and HLA-DQ8 heterozygotes (DQ8/x_OR = 0.99, 95% CI: 0.52-1.77, p = 0.99) displayed lower correlations with tTG-IgG positivity, suggesting a potential risk elevation for tTG-IgG positivity is associated with the combination of DQ2.5 and DQ2.2 or DQ8. Conclusions Our study indicates the risk gradient of HLA-DQ genes in IgA deficient patients. Overall, compared to patients without HLA-DQ2 or DQ8 haplotypes, the homozygous HLA-DQ2.5 genotype had the highest correlation with tTG-IgG positivity, followed by HLA-DQ2.5/DQ2.2 and HLA-DQ2.5/DQ8 heterodimers. The results suggest that HLA-DQ2.2 or HLA-DQ8 alone does not confer risk, but when in the presence of HLA-DQ2.5 these alleles may increase the risk for tTG-IgG positivity. Results from this study shed light on the risk of CeD in patients with IgA deficiency.

Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis

Background & AimsCurrent international guidelines recommend duodenal biopsies to confirm the diagnosis of coeliac disease in adult patients. However, growing evidence suggests that IgA anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict coeliac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of coeliac disease in adults. MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected coeliac disease. We used a bivariate random-effects model to calculate the summary estimates of sensitivity, specificity, positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value (PPV) of the no-biopsy approach across different pre-test probabilities of coeliac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. ResultsA total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven coeliac disease in the included studies was 62% (95% CI, 40% - 83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24% - 40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42% - 60%), and the summary specificity was 100% (95% CI, 98% - 100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 – 0.89). The PPV of the no-biopsy approach to identify patients with coeliac disease was 65%, 88%, 95%, and 99% if coeliac disease prevalence was 1%, 4%, 10% and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only one study had a low risk of bias across all domains. ConclusionThe results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pre-test probability of coeliac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

P01 An unusual case of pregnancy associated osteoporosis presenting with bilateral neck of femur fractures

P01 An unusual case of pregnancy associated osteoporosis presenting with bilateral neck of femur fractures

P17 A bend in the road: a patient with rheumatoid arthritis developing multicentric reticulohistiocytosis

P17 A bend in the road: a patient with rheumatoid arthritis developing multicentric reticulohistiocytosis

Serological Investigation of Persistent Villous Atrophy in Celiac Disease.

Persistent villous atrophy (VA) is not uncommon in celiac disease (CeD) while patients take a gluten-free diet (GFD). We conducted a retrospective study with 122 serum samples collected from controls and patients with CeD either at the initial diagnosis or at the follow-up during endoscopy. These samples were assigned to 3 groups: nonceliac control, non-VA CeD (Marsh score 0-2), and VA CeD (Marsh score 3a-3c). We established an in-house multiplex assay to identify potential serological biomarkers for VA. We assessed autoantibodies reported to affect the small intestine, including IgA and IgG antibodies against tissue transglutaminase (tTG), interferons, villin, actin, autoimmune enteropathy-related 75 kDa antigen (AIE-75), and tryptophan hydroxylase (TPH)-1, as well as 27 cytokines. The apolipoproteins quantified included apo A1, apo B-100, and apo A4, which were produced predominantly by the intestinal epithelium or expressed specifically in villi. Autoantibody levels were high only for tTG antibodies, which performed well in initial CeD diagnosis, but suboptimally for VA prediction during follow-up, because 14.6% of the follow-up patients with VA had low tTG-IgA. Increasing dilution improved tTG-IgA quantification, particularly when the antibody levels were extremely high but did not significantly improve VA detection. Among those with low tTG-IgA and persistent VA, high proinflammatory cytokines were observed in 2 patients. Median low-density lipoprotein cholesterol levels were significantly lower in the VA CeD group ( P = 0.03). Apolipoprotein levels were similar in patients with and without VA but diverged between those on a GFD or not. tTG-IgA as a biomarker is suboptimal for VA prediction while on a GFD. Persistent VA is associated with low low-density lipoprotein cholesterol levels and partially related to persistent high proinflammatory cytokines.

Assessment of autoantibodies in paediatric population with primary immunodeficiencies: a pilot study

BackgroundThe correlation between primary immunodeficiencies (PIDs) and autoimmunity shows ethnic and geographical diversity. The aim of our study was to accumulate more data in paediatric PID population.Methods58 children aged 1–17 and with PID (study group) and 14 age-matched immunocompetent individuals (control group) were included in the study. Serum levels of 17 different specific IgG antibodies against autoantigens were measured by means of a quantitative enzyme immunoassay. Immunoglobulin levels were analysed in relation to a detailed medical examination.ResultsAutoantibodies against one or more antigens were detected in the sera of 24.14% (n = 14) subjects in the study group. The most frequent were anti-thyroid peroxidase (anti-TPO) antibodies (n = 8; 13.8%). Anti-TPO antibody levels were elevated more often in PID patients with a positive family history of autoimmune diseases (p = 0.04). The screening for anti-deamidated gliadin peptide (DGP) and anti-tissue transglutaminase (tTG) antibodies in our series allowed identifying two previously undiagnosed cases of coeliac disease in PID patients. There was no statistically significant difference between the study and the control group in terms of the autoantibodies prevalence.ConclusionsThis study provides data on the prevalence of autoantibodies in paediatric population diagnosed with PID. Selected autoantibodies (i.e. anti-tTG, anti-DGP) might be useful for the screening of PID to avoid the delay of diagnosis of an autoimmune disease.

A223 UNMASKED OR INDUCED COLITIS: COULD IT BE SECUKINUMAB?

Abstract Background Spondyloarthropathies (SpA), such as Ankylosing Spondylitis (AS) are inflammatory disorders which have coheritability with inflammatory bowel disease (IBD). Secukinumab is a monoclonal antibody inhibitor of IL-17A used to treat SpA, but has also been reported to cause de novo and exacerbations of known IBD. Rare reports of Secukinumab induced microscopic colitis have also been documented. Purpose To present and discuss the diagnostic challenges in a case of undifferentiated colitis in a patient with AS treated with Secukinumab. Method Case report and literature review. Result(s) Case Report: A 62-year-old male with a history of AS was admitted to hospital with acute on chronic diarrhea. The patient’s AS was unresponsive to Infliximab, Methotrexate, and Adalimumab, although the latter improved his diarrhea at the time. A Colonoscopy completed 14 years earlier for chronic diarrhea was endoscopically normal with biopsies of the left colon notable for mild patchy inflammation and fibrosis. A subsequent Colonoscopy with random biopsies 8 years later showed normal mucosa while he was treated with Adalimumab. He was started on Secukinumab 4 months prior to hospitalization noting progressive watery diarrhea and weight loss of 15kg. Investigations were notable for microcytic anemia (Hemoglobin 120 g/L, MCV 78 fL), elevated CRP (33 mg/L), and a creatinine of 508 µmol/L. Negative tTg antibodies and normal IgA levels ruled out celiac disease. Stool studies were unremarkable. Colonoscopy showed several linear ulcerations in the descending colon and rectum with a normal terminal ileum, transverse, and ascending colon. Biopsies from the endoscopically normal mucosa showed thickened subepithelial collagen band suggestive of microscopic colitis while the ulcerated regions showed cryptic rupture with associated granuloma representing possible Crohn’s colitis versus drug-induced injury. Stains were negative for CMV. Secukinumab was stopped and he was started on Budesonide with significant improvement in symptoms. Literature Review Almost half of all patients with SpA have microscopic intestinal inflammation and of these, 7% eventually develop IBD. Shorter symptom duration, higher SpA activity and male sex are known risk factors for underlying intestinal involvement. However, the exact role of microscopic intestinal inflammation in SpA has yet to be determined. Secukinumab is an inhibitor of IL-17A with significant efficacy in the treatment of SpA but has been associated with exacerbations of Crohn’s disease and de novo cases of IBD. Thus, the role of IL-17 in IBD remains uncertain and may suggest a protective effect rather than an inflammatory one seen in SpA. The long half-life of Secukinumab (24-31 days) presents challenges when considering treatment with other biologics, such as anti-TNFs, which may cause excessive immunosuppression. Image Conclusion(s) New onset colitis is a described but rare entity in patients treated with Secukinumab presenting several diagnostic and treatment challenges. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Celiac Disease Screening in the Siblings of Pediatric Patients with a Confirmed Diagnosis: A Cross-sectional Study

Background: The close relatives of patients with celiac disease (CD), particularly their siblings, are known to be at a higher risk for CD development. Objectives: Our aim was to determine the prevalence of CD in siblings of confirmed CD patients in Lorestan province, Iran, in 2020. Methods: In this cross-sectional study, anti-tissue transglutaminase (tTG) antibody levels were measured in 140 siblings of children with CD. Duodenal biopsies were taken to confirm the diagnosis in those with positive serological tests. The subjects’ demographic and clinical data were recorded into a pre-designed questionnaire, and the collected data were analyzed by SPSS software version 22 at a significance level of 0.05. Results: Twelve out of 140 subjects (8.6%) tested positive for tTG IgA, eight of them (66.7%) were girls, and most of them (75%) were ≤ 15 years old. Half of the newly diagnosed patients were in the Marsh IIIc category. The Marsh grading had no significant relationship with the serum levels of tTG IgA antibodies (P = 0.319). The most common gastrointestinal symptom was bloating (66.7%), and the most common extraintestinal symptoms were anemia (58.3%) and dental and oral diseases (58.3%). Conclusions: We found a high prevalence (8.6%) of CD among the siblings of children with confirmed CD. Since the early diagnosis of CD can lead to better management, particularly in pediatrics, it is recommended screen patients’ family members as soon as the diagnosis of CD is confirmed.

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 &lt; 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 &lt; 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%.

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.

Tissuetransglutaminas antibodies in male and female celiac patiants, Wasit,Iraq

The current study included knowledge of the level of anti-tissue transglotaminasTtg (Ab) of both types (IgA-IgG) for males and females celiac patients. The study was conducted in the Public Health Laboratory in Wasit province, where they were diagnosed with celiac disease using measuring the level of Ttg antibodies with both types ( IgA), (IgG) by the ELIZA method. Then, the patients were divided into two groups. The first group included 35 male patients compared with another group that included 40 female patients, whose ages ranged from one year to more than 40 years for both genders.

Gluten-free diet adherence and implications for the diagnosis of coeliac disease

Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten containing foods in genetically susceptible individuals, with a worldwide prevalence of up to 1%. Currently, the only available treatment is a gluten-free diet (GFD). Screening for CD is primarily performed using serum based testing for anti-tissue transglutaminase (tTG) antibodies. Patients must be on a gluten containing diet at the time of testing to ensure an accurate serological result. We investigated the prevalence of a GFD in hospital clinic settings and the general population using survey data to estimate the proportion of CD patients that may be misdiagnosed for CD based on serological tests. Data were collected at clinics of a metropolitan hospital in Sydney, Australia, and the general population. Data from Medicare Benefits Scheme and tTG results from a large Australian private laboratory were reviewed for comparison. Of 778 participants who responded to the survey, 58 (7.5%) were on a GFD. More patients attending the immunology (15.9%) and gastroenterology (12.1%) clinics adopted a GFD than those attending the diabetes (2.6%) or endocrinology (6.1%) clinics, or in the general population (4.3%). More females than males excluded gluten from their diet (p<0.0001). Medicare statistics between 2013 and 2019 demonstrated an increase in CD serological testing; however, tTG data from a private pathology highlighted a stable level of elevated tTG antibodies of 3% of total tests performed. The high number of individuals on a GFD is likely impacting the ability to accurately diagnose CD using serum-based testing.

Relationship of citrulline and tissue transglutaminase antibody with duodenal histopathology among children with celiac disease

ObjectivesNon-invasive biomarkers, for the diagnosis of celiac disease, can reduce the need for biopsy, particularly in pediatric patients. The aim of this study was to investigate the levels tissue transglutaminase antibody (tTG) and plasma citrulline and its correlation with intestinal biopsy. MethodsIn this cross-sectional descriptive study, Pediatric patients with celiac disease referred to (XXX)were included. The patients underwent tTG antibody test along with plasma citrulline measurements using HPLC ((high performance liquid chromatography). Biopsy was performed in all the patients and clinical and demographic findings were recorded in a patient form. The data were statistically analyzed using SPSSv22. ResultsOf 118 patients with celiac disease, the mean level of citrulline in patients was 17.48 ± 6.92 and the mean tTG titer was 183.17 ± 41.25. The two variables were inversely correlated with each other, p < 0.01. With an increase in Marsh levels, a significant reduction in citrulline levels and an increase in plasma tTG levels were seen, p < 0.01, respectively. The mean citrulline and tTG titer was not associated with gender and the age of the patients. ConclusionOur findings indicate that citrulline and tTG antibody titer are significant biomarkers for the diagnosis of celiac disease and the severity of intestinal atrophy among pediatric patients.

Vitamin B12 (Cobalamin) Deficiency in Overt and Subclinical Primary Hypothyroidism.

Background:B12 (cobalamin) deficiency has been reported in hypothyroid patients with variable prevalence rates thus routine screening of hypothyroid patients was recommended by some and discouraged by others. We aimed to assess the prevalence of B12 deficiency among hypothyroid patients and to evaluate for pernicious anemia and celiac disease as etiologies.Methods:A total 133 patients were included. Thyroid hormones and thyroid peroxidase (TPO) autoantibodies were measured. Serum B12 was measured and if deficient, intrinsic factor antibodies (IFAB) and tissue transglutaminase (tTG) antibodies were evaluated.Results:Our study included 45 patients with overt hypothyroidism (OH), 48 patients with subclinical hypothyroidism (SCH), and 40 patients as controls. Mean age was 34.3 years and 82% were females. TPO antibodies were positive in 73.5% of OH and 51.1% of SCH patients. B12 deficiency was detected in 33.3%, 47.9%, and 37.5% of OH, SCH, and controls, respectively with no significant difference (P = .334). Borderline-to-low B12 level was more prevalent in the OH and the SCH groups compared to controls (68.9%, 85.4%, and 57.5%, respectively; P = .014). Among B12-deficient hypothyroid patients, 7.5% had positive IFAB and 13.3% had positive tTG antibodies. We did not find a significant association of TPO positivity and B12 deficiency (OR, 0.69; 95% CI 0.3-1.57; P = .147).Conclusion:We did not find a higher prevalence of B12 deficiency among hypothyroid patients nor an association with TPO positivity. Borderline B12 levels were more prevalent among hypothyroid patients.

S2867 Turmeric-Induced Hepatitis

Introduction: Dietary supplementation use has been on an exponential rise for the past few years. Turmeric is one of the most used, with curcumin being its major active ingredient. Recently, cases of turmeric induced autoimmune hepatitis as well as herbal induced liver injury (HILI) have been documented. We present a case of turmeric induced hepatotoxicity in a 64-year-old female. Case Description/Methods: A 64-year-old female with a history of hypertension, presents with jaundice and abdominal discomfort. Vitals were normal. Exam showed scleral icterus with an unremarkable abdominal exam. Lab findings revealed a normal CBC, INR, and a negative blood alcohol level, a total bilirubin of 13.6 mg/dl with a direct bilirubin of 9.2 mg/dl, an ALP of 248 IUnits/L, a GGT of 616 Units/L, an AST of 2789 IUnits/L, and an ALT of 3296 IUnits/L. Hepatitis panel with HEV were negative. ANA, AMA, ASMA, tTg antibody, Ig levels, TSH, and T4 were all negative or within normal limits. Patient had a normal iron saturation, negative ceruloplasmin, Tylenol and ASA levels. COVID19 PCR test was negative. CT abdomen/pelvis was non-diagnostic. An EGD/EUS/ERCP showed a mildly thickened gallbladder wall. Liver biopsy showed portal and lobular hepatitis with spotty necrosis, without evidence of an autoimmune process, suggesting a drug induced liver injury. Patient then admitted to the use of turmeric in the past 3-4 weeks. Turmeric was discontinued and patient’s lab values normalized within 1 month. Discussion: Turmeric has been used for thousands of years as a spice, and has been linked to antioxidant, anti-inflammatory and anti-cancer effects. Clinical studies have popularized its use for patients with immune disorders such as autoimmune thyroiditis, and rheumatoid arthritis, despite the associated risk of autoimmune hepatitis in such patients. Curcumin is the major active ingredient in turmeric, however when taken alone, it has a poor bioavailability, with extensive 1st pass metabolism. Turmeric contains Piperine (a black pepper extract), that augments and increases curcumin doses up to 2000-fold by inhibiting hepatic drug-metabolizing enzymes. Multiple RCTs have studied the safety of curcumin showing minimal side effects. In 2013, HILI accounted for 20% of drug-induced liver injury cases. Liver enzymes resolve within 1 month of discontinuation. Due to turmeric’s possible increased risk for hepatotoxicity, clinicians should highlight this to their patients and make them aware of the potential risks that exist when using turmeric.Figure 1.: 400x H&E stain): The portal areas are expanded by predominantly lymphocytic inflammation with scattered eosinophils and rare plasma cells. Figure 2 (400 x PAS): There is spotty necrosis. There is no steatosis, ballooned hepatocytes, granulomas, or viropathic changes. Figure 3 (400x): The Reticulum stain shows a mild increase in portal/periportal fibrosis.Table 1.: RUCAM (Roussel Uclaf Causality Assessment Method) Score: Method for detecting drug-induced liver injury or herb-induced liver/hepatocellular injury (modified) ALT: Alanine Transaminase, AST: Aspartate Transaminase, EBV: Epstein-Barr Virus, HSV: Herpes Simplex Virus, VZV: Varicella-Zoster Virus, PSC: Primary Sclerosing Cholangitis.

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.

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.

Maturity Onset Diabetes of the Young Masquerading as New Onset Diabetes Mellitus Type 1

Introduction:/background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders with autosomal dominant mode of inheritance. Mutation in hepatocyte nuclear factor-1β (HNF-1β) gene results in an error of embryonic development of pancreas and nephron, leading to MODY type 5. MODY 5 accounts for 1% of maturity-onset diabetes of the young. It has peak incidence in adolescence/early adulthood, and is associated with renal pathology. Clinical Case: A 15-year boy with history of hypertension and Hashimoto thyroiditis with normal thyroid function was referred for Hb A1C of 6.7% (< 6.4%). Physical exam was remarkable for normal weight at 64%, normal BMI at 83%, absence of thyromegaly or acanthosis nigricans. Diabetes was confirmed by 2 hour Oral Glucose Tolerance Test study (baseline glucose 154 mg/dL (<126 mg/dL), 2 hour glucose 384 mg/dL (<140 mg/dL)). Small doses of insulin (total daily dose 0.1 units/kg/day) resulted in good glucose control. Further labs were significant for weakly positive TTG and GAD antibodies (tTG Ab IgA 55.5 U/mL (<4.0 U/mL), GAD-65 Ab 0.05 nmol/L (< 0.02 nmol/L)), positive TPO (0.0 - 34.9 IU/mL) and detectable ATA antibodies 45.8 IU/mL (0.0 - 40.0 IU/mL), C-peptide 2.9 ng/mL (0.9–7.1 ng/mL). Islet cell, Insulin and Zinc transporter 8 antibodies were negative. Over the next few months he was weaned off insulin and subsequently he had a high insulin of 29.43 uU/mL (3.0 - 17.0 uU/mL) with glucose level of 169 mg/dL. Renal US was performed as part of the work up for hypertension and revealed a small right calculus with no hydronephrosis and a small 8-mm cortical cyst in the right kidney. Urinalysis showed microalbuminuria. Upper GI endoscopy and colonoscopy with biopsy ruled out celiac disease. Presumptive diagnosis of MODY was entertained despite positive TPO, ATA, TTG and GAD antibodies suggesting autoimmune endocrinopathies. His Hb A1C levels were in the range of 5.7 to 6 % during the 15 months of follow up. Genetic testing for MODY resulted in heterozygous deletion of exons 1–9 of the HNF1B gene consistent with MODY5. Conclusion: This is a case of MODY 5 with weakly positive GAD 65 antibodies that was initially misdiagnosed as type 1 diabetes. The presence of weakly positive antibodies should not preclude a work up for MODY in a patient who does not have the clinical features of classic type 1 DM.