IgA Anti-tissue Transglutaminase Antibodies Research Articles

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.

Vitamin D and celiac disease.

Celiac disease (CD) is an immune-mediated condition affecting the small intestine. Its reported global prevalence falls within the range of 0.7% to 1.4%. Notably, historically, higher rates, reaching 1% in Western Ireland, have been documented. Recent research has even revealed prevalence rates as elevated as 2% in northern Europe. These findings underscore the urgency for swift and cost-effective diagnosis, especially in individuals identified through screening efforts. At present, the diagnosis of CD relies on a multifaceted approach involving positive serological markers such as IgA anti-tissue transglutaminase (anti-TTG) and anti-endomysial antibodies (anti-EMA). These serological findings are assessed in conjunction with classical histological alterations, as outlined in the Marsh classification. CD is an inflammatory condition triggered by the consumption of gluten, resulting from intricate interactions between genetic, immunological, and environmental factors. CD is linked to malabsorption, leading to nutritional deficiencies. Individuals with CD are required to adhere to a gluten-free diet, which itself can lead to nutrient deficiencies. One such deficiency includes vitamin D, and there is substantial experimental evidence supporting the notion of a bidirectional relationship between CD and vitamin D status. A low level of vitamin D has a detrimental impact on the clinical course of the disease. Here we summarize the key characteristics of CD and explore the prominent roles of vitamin D in individuals with CD.

Prevalence of IgA Anti-tissue Transglutaminase Antibody in a Cohort of Iranians Patients with Inflammatory Bowel Disease

Abstract Background and Aims Some studies have reported the coexistence of inflammatory bowel disease (IBD) and celiac disease (CD). However, the prevalence of anti-tissue transglutaminase antibodies (IgA and IgG) and their screening value in patients with IBD is not yet clear. This study aimed to assess the prevalence of IgA anti-tTG and its potential correlation with disease status in patients with IBD. Materials and Methods This cross-sectional study was conducted on 110 patients with confirmed IBD diagnosis at Ghaem Hospital, Mashhad, Iran. For each patient, all demographic and clinical data including age, extra intestinal manifestations, underlying diseases, types of diseases, and surgical history were collected. IgA anti-tissue transglutaminase titers were assessed by enzyme-linked immunosorbent assay. Results None of the patients with IBD were positive for IgA anti-tTG antibodies, with a mean titer of 3.31 ± 1.3 AU/mL. Also, the mean titers were not associated with age, gender and various disease clinical features including the disease history, underlying disease, diagnosis type, extraintestinal manifestations, and surgery history. Conclusion No significant prevalence pattern of IgA anti-tTG antibody was observed in patients with IBD. Accordingly, serological screening for CeD is not recommended in IBD patients, unless in a relevant clinical CeD suspicion.

Sieving out non-celiac gluten sensitivity amongst patients with irritable bowel syndrome

ObjectivesIt is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity. Methods492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms. ResultsOf 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders. Conclusions12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice.

Helicobacter Pylori and Celiac Disease Antibody Positivity Have a Higher Prevalence in Patients With Distal Gastrectomy: A Cross-Sectional Retrospective Study.

Aims and objectives Distal gastrectomy was a widely used therapeutic option for peptic ulcer and gastroesophageal reflux disease until quite recently. The consequences of anatomical and physiological changes following surgery in the gastric mucosa have been the object of interest for the scientist. In this study, we aimed to determine whether Helicobacter pylori (HP) infection and celiac disease were more common in patients with a history of distal gastrectomy. Materials and methods This is an observational retrospective study conducted at Giresun University Faculty of Medicine. The medical files of 35 patients with dyspepsia who had a history of distal gastrectomy for benign etiologies (antrectomy group) and 50 patients with dyspepsia (control group) were retrospectively analyzed. Results There were more males and older patients in the antrectomy group. Concerning the lab parameters, platelets, lymphocyte, and albumin levels were significantly lower, and urea, creatinine, anti-Endomisium Ig A (anti-EMA), and anti-tissue transglutaminase IgA (anti-tTGA) antibody positivity were significantly higher in the antrectomy group. Gastric biopsy results revealed a higher positivity of HP, atrophy, neutrophil, and lymphocytes in the antrectomy group. Correlation analysis revealed an inverse correlation between albumin and anti-EMA/atrophy positivity whereas a positive correlation between anti-EMA and HP/atrophy positivity. Conclusions HP infection and coeliac disease (CD) could be the problems that distal gastrectomy patients with dyspepsia can face during their follow-up. Concerning the pre-malignant potential of HP, its screening and eradication should be performed to prevent the malignant transformation of the remnant gastric tissue.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Identification of celiac disease associated IgA nephropathy by IgA anti-tissue transglutaminase2 antibody deposits in archived formalin-fixed tissues.

The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant. Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.

Characteristics of Pediatric Celiac Disease in Southern West Virginia

Purpose Celiac disease (CD) is a disorder in which gluten ingestion triggers an autoimmune response causing inflammation and damage to the small intestine. With improved awareness and screening availability, prevalence and variation in clinical presentation have subsequently increased. Thus, our study identified the disease characteristics and presentation patterns of pediatric CD in southern West Virginia. Methods We retrospectively reviewed charts for pediatric patients (age <18 years) diagnosed with CD during a 10-year period at a tertiary care hospital. Results A total of 59 patients met inclusion criteria. The mean age of diagnosis was 10.0+4.6 years, with 61% of patients being female. One-third of cases were asymptomatic and diagnosed from screenings of patients with hypothyroidism or type 1 diabetes mellitus. In symptomatic patients (n=40), abdominal pain was the most common presenting symptoms (78%), followed by constipation (30%). Classical symptoms of diarrhea and failure to thrive/unexplained weight loss were less common (n=9). At diagnosis, anti-tissue transglutaminase (tTG) IgA antibodies and deamidated gliadin peptide IgG antibodies were both positive in 88% of cases, and endomysial antibodies were positive in 70% cases. One-year post-diagnosis clinic follow-up rate was 63%. A gluten-free diet improved symptoms and tTG IgA serology levels in all patients with follow-up. Conclusion Our data fills in the gap of the paucity of information available about CD in children from Appalachia. A high index of suspicion is required to screen and diagnose CD as many patients are either asymptomatic or lack classical findings. A gluten-free diet is a highly effective treatment, although follow-up after initial diagnosis remains a challenge.

İlaç alerjisi olan hastalarda otoantikor sıklığı

Introduction: This study is aimed to analyze the autoantibody frequency in patients with drug allergy. Descriptive, observational research on drug allergy will contribute to the creation of new hypotheses about the pathophysiology of autoimmunity.Methods: The data of patients who were registered in the Training and Research Hospital database until the end of December 31, 2018 and diagnosed with drug allergy were retrospectively evaluated. Overall, 617 adult patients who had been diagnosed as “allergy status to drugs,” according to ICD 10, and had had at least one autoantibody result were included in the study.Results: The frequency of having at least one autoantibody varied between 0% and 92.1%. The most commonly detected autoantibody was rheumatoid factor (RF) (n = 241; 92.1%). The second most common one was anti-tissue transglutaminase IgA antibody (Anti-tTG-IgA) (n=22; 68.2%). The frequencies of anti-thyroglobulin (Anti-TG), anti-thyroid peroxidase (anti-TPO), and anti-double stranded DNA (Anti-dsDNA) were 65.2% (n = 155), 59.7% (n = 159), and 43.6% (n= 55), respectively.Conclusions: Many drugs can trigger the development of autoantibodies with no progression to autoimmune disease. Autoantibodies should be suspected in patients with allergies to medications. Observational research on drug allergy will contribute to the creation of new hypotheses about the pathophysiology of autoimmunity. Numerous studies in this area can enable us to discuss the widespread use of risky drugs in a more objective way. We think that our study will shed light on the relationship between drug reaction and autoimmune diseases.Keywords: Autoantibodies, autoimmunity, drug allergy, drug hypersensitivity

"Long-term follow-up and prognosis of celiac hepatitis".

Celiac disease has been associated with abnormal liver function tests at diagnosis that usually resolve with a gluten-free diet (GFD). The aim of this study was to assess the evolution of liver involvement and possible long-term complications in patients on a GFD. Retrospective and single-center study, which included all individuals with Celiac disease followed in specialized consultation in a tertiary referral hospital. A total of 162 patients were included, most of them female (77.8%) with a median age of 24 years (IQR, 7-39). Seventy-four (45.7%) patients had abnormal liver function tests at diagnosis. These individuals had higher anti-tissue transglutaminase IgA (tTG-IgA) antibody titers (126 vs. 29 IU/L; P = 0.003). There were no significant differences in the Marsh classification ( P = 0.599). During follow-up, most celiac hepatitis patients had normalization of liver function tests and tTG-IgA antibodies. At the last follow-up, all the patients had fibrosis-4 index <2.4 and an aspartate aminotransferase-to-platelet ratio index score <0.6. Vibration-controlled transient elastography showed values <6.4 kPa in all cases. On the other hand, it was found that 42.9% of the individuals had a controlled attenuation parameter >206.5 db/m. In our cohort, liver function tests normalized in the vast majority of celiac hepatitis patients on a GFD, with no progression to chronic liver disease. It should be noted the high number of individuals who present hepatic steatosis during follow-up, which may be related to a diet that tends to be hyperlipidemic and hypercaloric.

Diagnostic Accuracy of Serum Anti-Tissue Transglutaminase Antibody in Diagnosis of Pediatric Celiac Disease

Background: Celiac disease (CD) is an immune mediated enteropathy that is caused by intolerance to gluten storage protein of wheat bartey and rice. Early diagnosis of celiac disease is highly imperative to institute early intervention in order to prevent profound macronutrient deficiencies as well as long term complications. Diagnostic investigation for celiac disease, the matter of controversy, with endoscopic duodenal biopsy remaining the gold standard but invasive, costly, painful, needing expertise and carrying risks of endoscopy, while serologic tests although noninvasive, cheap, easily available but with disputed specificity and sensitivity. Objective: To find the accuracy and importance of anti-tissue transglutaminase IgA antibody in celiac disease diagnosis and determination in pediatric patients. Place and Duration of Study: Department of Pediatrics, GMMMC Hospital Sukkur from 1st June 2019 to 30th November 2019. Methodology: One hundred and fifty children were suspected celiac diseases were enrolled. Demographic data including age, gender was noted. Duodenal biopsy and upper GI endoscopy of all patients with positive anti-tTG was performed. At least 6 biopsy specimens were taken from first and second part of duodenum and duodenal bulb. Results: Mean age of the children was 8.72±1.92 years. Sensitivity, specificity, PPV and NPV of tTG-IgA in evaluating celiac disease was 86.9%, 84.8%, 88%, 83.6% and 86% respectively. Conclusion: Tissue transglutamianse (TTG) is an excellent screening test for celiac disease in high risk Paediatric population having diagnostic accuracy of 86%. Therefore, it can be safely recommended that patients having even fewer clinical features should be screened by TTG to detect celiac disease patients with minimal signs and symptoms. Keywords: Celiac disease, IgA anti-tissue transglutaminase, Gastrointestinal endoscopy

Who to screen and how to screen for celiac disease

Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc.) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down’s syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD.

The utility of both anti-deaminated gliadin IgG and anti-tissue transglutaminase IgA antibodies for the diagnosis of coeliac disease without biopsy

Aim: To determine the utility of deaminated gliadin peptide IgG antibodies (DGP-IgG) as a replacement for endomysial antibodies to diagnose coeliac disease in children with a tissue transglutaminase IgA antibodies (tTG-IgA) ≥10× upper limit of normal (ULN).

Celiac disease may be rare among children in South China.

ObjectiveThe prevalence of celiac disease (CD) varies geographically and ethnically; however, the prevalence among children in South China remains unknown. We therefore determined the occurrence of CD among Chinese children in South China.MethodsSerum samples were collected from children and assessed for anti-tissue transglutaminase IgA antibodies (anti-tTG-IgA) and total IgA. Anti-tTG-IgA+ participants underwent human leukocyte antigen (HLA) DQ2/DQ8 determination. Samples with serum total IgA <0.05 g/L were also analyzed for anti-tTG-IgG, and for HLA-DQ2/DQ8 if the values were above borderline. Participants who were anti-tTG-IgA/IgG+ and HLA-DQ2+ and/or HLA-DQ8+ underwent small bowel biopsy.ResultsA total of 8794 children were enrolled, of whom 479 had chronic unexplained abdominal symptoms. Three (0.034%) children were anti-tTG-IgA+ and ten (0.114%) had serum total IgA <0.05 g/L, all of whom were anti-tTG-IgG−. The three positive children were all HLA-DQ2+ and/or HLA-DQ8+. Two underwent gastroscopy, and histopathology of small intestinal biopsy showed duodenal villous blunting in one and increased intraepithelial lymphocytes in the other, neither consistent with a diagnosis of CD.ConclusionOur study showed a prevalence of CD autoimmunity of 0.034% and failed to identify any cases of CD, suggesting a low prevalence of CD among children in South China.

Stanovení lepku ve stolici jako metoda k ověření compliance s bezlepkovou dietou u dětí s nově dia gnostikovanou celiakií

Objectives and study: To compare the values of gluten-related immunogenic peptides (GIP) in stool and anti-tissue transglutaminase IgA antibodies (anti-tTG IgA) in blood in children newly diagnosed with coeliac disease (CD). Methods: All children (2–15 y) newly diagnosed with CD between May 2018 and May 2020 at our clinic who complied with the inclusion criteria were invited to join the prospective study. During workup for CD, a stool sample to measure GIP was taken together with a blood sample to measure anti-tTG IgA. All newly diagnosed children were invited 4 months later for a check-up. Children and their caregivers were asked about known non-compliance with the gluten-free diet (GFD), a blood sample was taken to measure the anti-tTG IgA, and a stool sample was collected to measure GIP. Blood was evaluated for anti-tTG IgA by ELISA, and the stool was tested by quantitative Sandwich ELISA designed to detect and quantify GIP using the G12 antibody. Values of GIP and anti-tTG IgA were compared in terms of their relation to the upper limit of normal (ULN) of the particular method. Results: 29 children (18 girls) were enrolled in the study. The values of GIP in stool at the time of diagnosis were above the ULN (0.15 µg/g) in all children. Average 4.21, median 3.29, standard deviation (SD) 3.7. After the four months, all but three (89.7%) had values of GIP in the reference range. Average 0.29, median 0.12, SD 0.73. Similarly, anti-tTG IgA values were above the ULN (9.9 U/mL) at the time of diagnosis in all children. Average 164, median 195, SD 49. Although the anti-tTG IgA levels were lower at check-up in all but one child, only 10 (34.5%) showed values within the normal range, with an average of 27.9, median 12.0, and SD 38.9. All children declared strict adherence to GFD. Discussion: Using the GIP concentration in stool, adherence to GFD in our cohort of children is very good, better than that described in literature. Conclusion: Measuring GIP in stool could prove a more sensitive indicator of adherence to GFD in the early months after the diagnosis of CD when anti-tTG IgA are still elevated above the ULN due to their well-described gradual decrease after GFD initiation.

Serum anti-tissue transglutaminase IgA antibodies in patients with psoriasis vulgaris and relation to its severity

Serum anti-tissue transglutaminase IgA antibodies in patients with psoriasis vulgaris and relation to its severity

Screening for Celiac Disease in Patients with Irritable Bowel Syndrome Fulfilling Rome III Criteria

Abstract Background Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Celiac disease (CD), a treatable autoimmune enteropathy, with varied presentations, may simulate clinically symptoms of IBS. The aim of the present study is to screen for CD in patients with IBS diagnosed based on the Rome III criteria. Patients and Methods A cross-sectional study was conducted at a secondary care gastrointestinal unit in Al-Salam General Hospital in Mosul city, Iraq, from November 2015 to October 2016. All patients fulfilling the Rome III criteria for IBS were screened for CD using antitissue transglutaminase IgA antibodies (anti-tTG). Patients who tested positive were subjected to endoscopic duodenal biopsy to confirm the diagnosis of CD. Results A total of 100 patients were included in the present study (58 female and 42 male), the mean age of the participants was 40.8 years old (standard deviation [SD] ± 11.57). Ten patients (10/100, 10%) tested positive for anti-tTG antibodies. Five of the seropositive patients (5/10, 50%) showed positive biopsy results according to the Marsh classification, 3 of whom having diarrhea, and 2 with constipation. Conclusion Positive serology and biopsy results suggestive of CD are common among patients with IBS. Screening patients with IBS for CD is justified.

Celiac disease associated liver dysfunction: Study of the histological features and co-localisation patterns of IgA and IgG anti-tissue transglutaminase antibody (TTG-2) in liver biopsies

Celiac disease (CeD) associated liver dysfunctions (CALD) have wide range of manifestation ranging from milder symptoms alleviating on gluten free diet (GFD), to pathological conditions such as autoimmune hepatitis, cirrhosis etc. However, characteristic histopathological signatures diagnostic of this entity have not been described yet. Diagnosis relies solely on clinical suspicion due to co-occurrence of two pathologies. The aim of this study is to elucidate histological features of CALD and demonstrate IgA/IgG anti-tTG colocalization patterns as a hypothetic evidence towards etiology. 28 formalin fixed paraffin embedded (FFPE) core liver biopsies from patients with treatment naïve CeD with associated liver dysfunction and another 5 FFPE liver core biopsies from patients with other proven pathologies and normal serum anti-tTG titres, were retrieved and IgA/IgG anti-tTG colocalization was carried out both by dual immunohistochemistry (IHC) and dual confocal immunofluorescence (IF) techniques. After a period of GFD, clinically indicated liver biopsies from 5 of these 28 patients were obtained and subjected to repeat testing via the same techniques. Histopathological examination in CALD revealed the following spectrum: steatohepatitis 4 (14.2%), autoimmune hepatitis 4 (14.2%), non-cirrhotic portal venopathy 1 (3.5%), secondary hemochromatosis 1 (3.5%), steatohepatitis with necrotising granuloma 1 (3.5%), cirrhosis 3 (10.7%), irregular sinusoidal dilatation 14 (50%). In CALD, IgA/IgG anti-tTG colocalization was noted in 85.6% cases by dual IHC technique and in 92.8% cases by dual IF technique. Follow up biopsies in 5 CeD cases showed no co-localisation. Deposition of the circulating IgA/IgG anti-tTG antibodies in suspected patients of CALD seems to be a sensitive and specific technique for diagnosing their celiac association, thereby opening up newer insights into management protocols.

Response of Hepatitis B Vaccine in Children with Celiac Disease – An Experience at Ayub Teaching Hospital, Abbottabad Pakistan

Background: Celiac Disease (CD), characterized by chronic small intestinal inflammation, is an immune-mediated disorder, with a strong family history and association with DQ2 HLA haplotype. It has been postulated that children with CD show less response to hepatitis B vaccine due to overexpression of HLA-DQ2 haplotype. This study was done to determine the response of hepatitis B vaccine in children with CD in our tertiary care setting in the Hazara region of eastern Khyber Pakhtunkhwa, Pakistan.Material and Methods: This cross-sectional study was conducted in the Pediatrics outpatient department (OPD) of Ayub Teaching Hospital, Abbottabad Pakistan from April 2018 till March 2020. Children with CD (n=38) aged 1-14 years with completed HBV vaccination, anti-tissue transglutaminase IgA antibody (tTG-IgA) &gt;150 IU/ml and/or typical histological findings of CD on small-bowel biopsy, were included in the study. Hepatitis B surface antibody (HbsAb) titer of ≥10 mIU/ml was taken as antibody positive, while HbsAb levels &lt; 10 mIU/ml were considered as vaccine non-responsive. Data was analyzed using SPSS version 20.0. Chi square test was applied for comparison with P-value &lt; .05 taken as significant.Results: Out of 38 diagnosed cases of CD, 15 (39.5%) were males and 23 (60.5%) were females. Mean age of children was 8.32±3.26 years with an age range of 3-14 years. HbsAb levels ranged from 0.10 to 62.7 mIU/ml with a mean of 11.2+17.42 mIU/ml. HbsAb levels were less than 10.0 IU/ml in 73.7% of children with CD. Small intestinal biopsy was performed in 11 (28.9%) patients. There was a significant relationship between anti tTG-IgA levels and histopathology findings with P-value of .001.Conclusions: In children having celiac disease, there was low rate of protective antibody response to hepatitis B vaccine.

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.