anti-tTG IgA Research Articles

Reliability of the Multiplex CytoBead CeliAK Immunoassay to Assess Anti-tTG IgA for Celiac Disease Screening.

Background and Objective: The diagnosis of Celiac Disease (CD) is first based on the positivity for specific serological markers. The CytoBead CeliAK immunoassay simultaneously measures antibodies (IgA) directed to tissue transglutaminase (tTG), endomysium (EMA), and deamidated gliadin (DG), in addition to providing a control for total IgA levels. The aim of this study is to assess the reliability of this multiplex assay to detect anti-tTG IgA positive patients, compared with a conventional single-parameter enzyme-linked immunosorbent assay (ELISA).Methods: Serum samples from 149 pediatric patients were assessed by both CytoBead CeliAK immunoassay and ELISA, in order to evaluate their concordance for the measurement of anti-tTG IgA.Results: The measurement of anti-tTG IgA by CytoBead CeliAK immunoassay basically showed a complete concordance rate with the conventional and single-parameter ELISA, according to the respective cutoff values (3 U/ml and 10 U/ml).Conclusions: Our comparative analysis demonstrates a substantial equivalency between multiplex CytoBead CeliAK assay and the single-parameter conventional ELISA to assess anti-tTG IgA antibody in the context of the screening for CD in children. Importantly, CytoBead CeliAK assay could present some preanalytic, analytic, and economic advantages.

Prevalence of celiac disease in patients with atypical presentations

Background and study aimsUnawareness about atypical forms of celiac disease (CD) leads to the underdiagnoses of CD. This study has investigated the prevalence of CD in patients with atypical presentations, such as idiopathic low bone mineral density (ILBMD) and dyspepsia, in the Iranian population. Patients and methodsTwo separate groups of patients who have been diagnosed with dyspepsia and ILBMD (including either osteopenia or osteoporosis of unknown cause) were screened for CD during 2016–2019. Patients were serologically screened by means of IgA anti-tissue transglutaminase (IgA anti-tTG); in case of positive results, the patients underwent endoscopic intestinal biopsy to confirm the diagnosis of CD. ResultsOf 200 patients with ILBMD, six (3%) had a positive result for IgA anti-tTG; in five cases (2.5%), duodenal histology confirmed the CD diagnosis. Of 290 patients with dyspepsia, 25 (8.6%) had a positive result for anti-tTG IgA; nine cases (3.7%) were histologically compatible with CD. No significant differences were found between the two groups of patients. ConclusionsThe prevalence of CD in patients with atypical presentations, such as ILBMD and dyspepsia, is consistent (pvalue = 0.788) and higher than that in the general population (p value = 0.001); therefore, screening program for CD in these patients is highly recommended.

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

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

Evaluation of a Bi-Analyte Immunoblot as a Useful Tool for Diagnosing Dermatitis Herpetiformis.

Immune responses to tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are associated with dermatitis herpetiformis (DH), a gluten-related dermatosis. Recently, a bi-analyte immunoblot (b-aIB) was introduced to detect IgA antibodies in response to tTG and npG. We compared the utility of ELISA and b-aIB with tTG in serological diagnoses of DH and their agreement with direct immunofluorescence (DIF). In total, 55 sera (27 DIF-positive DH patients, 4 DIF-negative DH patients and 24 healthy controls) were examined. ELISA for anti-tTG IgA, b-aIB for anti-npG and anti-tTG IgA, and statistical analysis were performed. The b-aIB with tTG showed 78% sensitivity, 100% specificity, 100% positive predictive value, and 82% negative predictive value in relation to ELISA. A better rate of agreement (Cohen’s kappa values) in IgA detection was observed in the pair tTG ELISA and b-aIB with npG (0.85) than in pairs tTG ELISA and b-aIB with tTG (0.78) or b-aIB with tTG and b-aIB with npG (0.78). No degree of agreement was found between serological tests and DIF. Both serological tests may be used to detect the anti-tTG IgA in DH patients. Still, DH diagnosing requires careful consideration of clinical data as well as results of tissue imaging (crucial DIF) and immunoserological techniques detecting DH-type features.

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) >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 < 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 < .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.

Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres?

ObjectiveAvoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather...

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 < 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.

Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study

BackgroundCeliac disease (CD) is an autoimmune enteropathy in which HLA-DQ haplotypes define susceptibility. Our aim was to evaluate if belonging to a certain HLA-DQ class risk could be associated to the clinical, serological and histological presentation of CD.MethodsWe performed a retrospective observational monocentric study including all 300 patients diagnosed with CD, who underwent HLA typing. Clinical, serological and histological data was collected from clinical records and their association with HLA-DQ class risk was verified through statistical tests.ResultsIn our sample mean age at onset was 6.7 ± 4.2 years, with a prevalence of females (n = 183; 61%), typical symptoms (n = 242; 80.6%) and anti-tTG IgA ≥ 100 U/mL (n = 194; 64.7%). Family history was present only in 19% (n = 57) of patients, and it was not significantly associated with any of the clinical and demographical data analyzed or the belonging to a certain HLA-DQ class risk. We found in the male population more frequently a coexistence of CD and atopic syndrome (males: n = 47; 40.2%; females: n = 50; 27.3%; p = 0.020).Early age of onset, instead, was associated with typical symptoms (m = 6.4 ± 4; p = 0.045) and elevated liver enzymes (m = 5 ± 3.8; p < 0.001), while later age of onset was associated with presence of other autoimmune diseases (m = 8.2 ± 4; p = 0.01).We observed statistically significant influences of HLA class risk on antibodies and liver enzymes levels: G1, G4 and G2 classes showed more frequently anti-tTG IgA ≥ 100 U/mL (n = 44; 80%, n = 16; 69.6%, n = 48; 67.6% respectively; p-value = 0.037), and in patients from G2 class we found enhanced liver enzymes (n = 28; 39.4%; p-value = 0.005). HLA class risk was still significantly associated with anti-tTG ≥ 100 (p = 0.044) and with hypertransaminasemia (p = 0.010) after a multiple logistic regression adjusted for the effect of gender, age at onset and family history.ConclusionsWe failed to prove an association between HLA-DQ genotypes and the clinical features in our CD pediatric patients. Although, our results suggest an effect of the DQB1–02 allele not only on the level of antibodies to tTG, but possibly also on liver involvement.

Low Titer Tissue Transglutaminase Antibodies: A Link to Helicobacter pylori Infection?

Introduction: Low serum titer of anti-tissue transglutaminase (tTG) has been described in various conditions without any evidence of celiac disease (CD). Infectious agents have been suggested to trigger autoimmunity and promote the production of anti-tTG. The aim of this study was to investigate if there is a link between a positive celiac serology and concomitant Helicobacter pylori infection in children. Methods: The data of 178 pediatric patients who underwent upper gastrointestinal endoscopy due to positive celiac serology were compiled. The patients whose histopathologic findings were not consistent with CD were followed on gluten-containing diet. The changes in the serum level of anti-tTG IgA on the follow-up were compared between H. pylori-infected and noninfected patients after the eradication of H. pylori. Results: Of 155 patients who met the inclusion criteria, 119 (group 1) were diagnosed as CD, and duodenal histopathology of the remaining 36 children (group 2) was not compatible with CD. In group 2, 11 out of 36 (30.5%) patients were infected with H. pylori. After the eradication of H. pylori, anti-tTG IgA level either decreased or dropped below cutoff value in 9/11 (81%) patients while it was 20% in those who were not infected with H. pylori in the 6th month of the follow-up (p = 0.001). Conclusion: Our results suggest that H. pylori infection may be the cause of false or transient positive celiac serology. Thus, a positive celiac serology should be carefully interpreted in the presence of H. pylori infection before confirming the diagnosis of this life-long disease.

Progression of pediatric celiac disease from potential celiac disease to celiac disease: a retrospective cohort study

BackgroundA subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease.MethodsWe performed a retrospective analysis of children (0–18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children’s Hospital between 2013 and 2018.ResultsThree hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6–5) X upper limit of normal (ULN) vs. 6.41 (3.4–10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6–5) X ULN to 3.6 (3.1–9.2) X ULN between biopsies.ConclusionsFour percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.

P78.11 Immunotherapy-Induced Coeliac Disease in the Curative Lung Cancer Patient on Adjuvant Durvalumab

The PACIFIC study led to the approval of durvalumab in the adjuvant setting for patients with unresectable, stage III non-small cell lung cancer (NSCLC) after chemo-radiotherapy (CRT)1, and whose tumours express programmed death-ligand-1 (PDL-1) in >1% of cells. PDL-1 is an immune regulating molecule which has been hypothesized to aid neoplastic lesions to evade the host’s immune system. Durvalumab is a human monoclonal IgG1 antibody which blocks PDL-1 on cytotoxic T-cells, leading to increased cytotoxic T-cell proliferation and activity, and cytokine production1. The activation of T-cells can lead to immune-related adverse events (IrAEs). A 68-year-old female with stage III NSCLC received adjuvant durvalumab. Her PDL-1 was 90-100%. After four cycles of durvalumab, she presented with Grade 2 diarrhoea2. She was admitted to hospital and started on prednisone 50mg (1mg/kg). After three days, she had a sigmoidoscopy which appeared macroscopically normal. Biopsies showed a non-specific increase in intraepithelial lymphocytes. The diarrhoea resolved, and she was discharged on a weaning regime of prednisolone for presumed immune checkpoint inhibitor (ICPi)-induced colitis. Two months later, she represented with Grade 3 diarrhea2. Examination and imaging was normal. Positive findings were an elevated serum anti-transglutaminase (anti-tTG) IgA level at 10.2unit/mL, low folic acid and low vitamin D. An oesophagogastroduodenoscopy (OGD) showed scalloping of the duodenum and biopsies showed marked villous blunting, chronic inflammation of the lamina propria and increased intraepithelial lymphocytes; all findings consistent with the diagnosis of CD. She was started on a lifelong gluten-free (GF) diet and given a weaning course of oral prednisone with the intention of improving her symptoms rapidly. Her diarrhoea immediately improved and a decision was made to restart immunotherapy once the steroids were complete. She did not report recurrence of her symptoms following an additional seven cycles of durvalumab therapy whilst on a GF diet. The anti-tTG IgA normalised after 3 months. This case highlights a rare IrAE of CD presenting during ICPi treatment. Durvalumab may have unmasked previously undiagnosed CD. Alternatively, the patient may have developed CD de-novo, as a direct consequence of ICPi treatment. The detection of rare toxicities requires a large number of patients to be treated with ICPis, therefore rarer toxicities are often identified post licensing, when the number of patients receiving these drugs increases exponentially. There are three published cases of patients receiving immunotherapy developing CD after the commencement of the drug but the exact incidence of this IrAE and exact underlying mechanism for the development of CD secondary to immunotherapy is unknown. This is the first reported case of CD arising following ICPis in both the adjuvant lung cancer setting, and with the drug durvalumab. A new diagnosis of CD will have long-term consequences for this patient who may have been cured with CRT alone. However, the majority of patients with stage III NSCLC have disease progression despite CRT and therefore the addition of immunotherapy in improving survival is significant. Although diarrhoea due to CD is an exceptional IrAE, symptoms can resolve quickly once a diagnosis is made and a GF diet commenced.

Frequency of Celiac Disease and Spontaneous Normalization Rate of Celiac Serology in Children and Adolescent Patients with Type 1 Diabetes

Objective:The prevalence of celiac disease (CD) varies between 1% and 10% in patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the frequency of spontaneous recovery of celiac serology and the biopsy-proven CD (BPCD) frequency in patients with T1DM.Methods:The data of 668 patients with available celiac serology tests from a total of 779 patients who were followed for the last 10 years with the diagnosis of T1DM were retrospectively evaluated.Results:Positive serology was detected in 103 out of 668 (15.4%) patients. There was spontaneous normalization in 24 (23.3%), fluctuation in 11 (10.7%) and permanently positive serology in 68 (66%). In 46 out of 53 (86.8%) patients with positive serology and biopsy, CD diagnosis was confirmed by biopsy (BPCD). The frequency of BPCD was 6.9%, and the serology in 76.1% was positive at the time of diagnosis of T1DM. The weight, height and body mass index-standard deviation score at diagnosis were lower in patients with BPCD compared to the group without CD. An anti-tissue transglutaminase-IgA (anti-TTG-IgA) level of 11.8 times the upper limit of normal was the most sensitive (93%) and specific (90%) cut-off for BPCD (area under the curve: 0.95; 95% confidence interval: 0.912-1; p<0.001).Conclusion:In our cohort, the frequency of positive serology for CD was 15.4%, while the rate of BPCD was 6.9%. The majority (97.8%) of cases were diagnosed within the first five years of T1DM. In 23.3% of cases, positive anti-TTG-IgA spontaneously resolved without a gluten-free diet (GFD). Therefore, serological follow-up instead of immediate duodenal biopsy or GFD therapy, particularly for patients with asymptomatic and mild anti-TTG IgA level, is warranted.

Screening for celiac disease among patients of the gastroenterological profile

To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection. 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males 24.9%; 1019 females 75.1%). The average age was 40.415.4 (1886 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA). In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA in 54 (4.4%), and anti-TTG IgG in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron 33%, hypoproteinemia 12.6%, hypoalbuminemia 12%, hypokalemia 5.48%, hypocalcemia 21.9%. An increase in the level of AST 14.5%, ALT 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities. The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

The impact of celiac disease and duration of gluten free diet on anterior and posterior ocular structures: Ocular imaging based study.

To evaluate the eyes of adult celiac disease (CD) patients and investigate the association between these ocular parameters with celiac specific antibodies and duration of gluten free diet (GFD). This cross-sectional study included 72 eyes of 36 CD patients (18-51 years of age) and 70 eyes of 35 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were scanned by a Scheimpflug camera, specular microscopy and spectral domain optical coherence tomography. Endothelial cell density (ECD), anterior chamber angle (ACA) degrees, anterior chamber depth (ACD), anterior chamber volume (ACV) and central macular thickness (CMT) values were lower in CD patients as compared with control group (p values = 0.038, 0.024, 0.002, 0.038 and 0.046 respectively). ECD and CMT were lower in celiac patients whom endomysial antibodies (EMA) IgA were positive (p = 0.001, p = 0.042 respectively). Tissue transglutaminase IgA antibody (anti tTG IgA) was weakly positively correlated (p > 0.05) with ACD, and positively (r = 0.319; p < 0.05) correlated with ACV. As the duration of compliance to the diet increased in the celiac group the mean and inferior retinal nerve fiber layer (RNFL) thickness decreased (p = 0.035, p = 0.008 respectively). Mean, inferior and temporal RNFL thicknesses were lower in celiac patients whose duration of GFD was longer than 5 years (p < 0.05). Decreases in ECD, ACA degree, ACD, ACV and CMT can occur in CD patients. In adult celiac patients; ECD, CMT might be effected in the presence of positive EMA, and ACD, ACV might be effected in the presence of higher anti tTG IgA titer. Adult celiac patients who had longer duration of GFD may have thinner RNFL. RNFL may be thinner in celiac patients who comply with GFD for more than 5 years.

Transient positivity of anti-tissue transglutaminase IgA autoantibody in febrile children: a case-control study.

Fever is a physiological response activated by integrative interactions between the neuronal and immune systems. The association of fever with the development of autoantibodies against various self-antigens is controversial. We here evaluated if fever was associated with increased levels of anti-tissue transglutaminase (tTG) IgA autoreactive antibodies in children. This was a case-control study performed the Amir-Al-Momenin Hospital of Zabol City from January to December 2018. Febrile children (N=135) and apparently healthy counterparts (N=135) were included. Total IgA and anti-tTG IgA were measured by ELISA. From 270 children evaluated, 144 (53.6%) and 126 (46.4%) were males and females, respectively. The mean age was 4.7 ± 2.6 years. The mean total IgA titer was 208 ± 100 mg/dl, and the mean anti-tTG IgA titer was 15.9 ± 68 mg/dl. There was a significant difference in the mean titer of anti-tTG IgA between apparently healthy controls (1.97 ± 1.12 mg/dl) and febrile children (30.2 ± 94.9 mg/dl, p=0.002). Positivity for anti-tTG IgA was observed in 16 (11.8%) out of 135 febrile children while no subject in the control group had positive results. One out of the 16 positive cases showed persistent elevated levels after fever disappearance. On biopsy examination, this child was confirmed to have celiac disease. We showed that fever can trigger the production of anti-tTG IgA autoantibody in children. It is recommended for pediatricians to be vigilant in interpreting anti-tTG IgA results during fever episodes and repeat positive cases after the cease of fever. It is also recommended to reassess anti-tTG IgA seropositivity in other clinical settings in future studies.

Morphological evaluation of bulb and distal duodenal biopsies in pediatric celiac disease with clinical and serological correlation.

An early correct diagnosis of celiac disease (CD) is fundamental to reversal of symptoms and prevention of complications in pediatric patients. Our aim was to evaluate the role of duodenal bulb biopsy by studying the degree of mucosal damage in the duodenal bulb (D1) and second part of the duodenum (D2) and correlating the findings with serum IgA anti-tTG levels. Pediatric patients (age <18 years) with clinical suspicion of CD and positive IgA anti-tTG titers were consecutively enrolled over a period of one year. Demographic variables, anthropometry, clinical history, laboratory values and endoscopic findings were studied. Endoscopic biopsies obtained from D1 and D2 were evaluated and assigned histopathologic grades that were correlated with serology. Descriptive statistics were employed. A total of 37 clinically suspected cases of pediatric CD were studied. The mean age was 6.7 years and the M:F ratio was 1:1.3. Thirty-two (32) children had varying degrees of growth impairment. Eight (8) children had only extra-intestinal symptoms. Thirty (30) children were anemic, hypoalbuminemia was seen in five (5) children while transaminitis was seen in two (2) children. IgA anti-tTG >300 U/ml was associated with Marsh-Oberhuber Grade 3 morphology at atleast one site. Low positive serology values should be confirmed by histopathology. Biopsies should be taken even in the absence of endoscopic abnormality. Additional D1 biopsies placed in a separate container can increase the diagnostic yield.

“Strongyloides stercoralis infestation in a severely malnourished (SAM) celiac disease child:” A rare case report from Western Rajasthan

A case of Strongyloides stercoralis infection in severe protein energy malnutrition child with associated celiac disease (CD) is herein reported. The case was a 4-year-old, severely malnourished female admitted to the tertiary level hospital of Western Rajasthan, due to watery diarrhea, pain abdomen, and vomiting, not responding to treatment. The patient was HIV negative, nondiabetic, had no evidence of tuberculosis, Liver Function Test, Renal Function Test were normal was within normal limits. She had microcytic hypochromic anemia, hypoalbuminemia, and serum Antitissue transglutaminase (anti tTG IgA)was 301.35 U/ML which confirmed the diagnosis of CD. Stool parasitological examination revealed numerous rhabditiform larvae of threadworm “S. stercoralis.” After treatment with gluten free diet and Albendazole and Ivermectin, the patient recovered without evidence of S. stercoralis in follow-up stool samples.

Prevalence of organ-specific autoantibodies in children with type 1 DM in south central region of India

Introduction: Type 1 diabetes mellitus (T1DM) is a long-standing metabolic disease caused by autoimmune beta cell destruction leading to absence or lowered insulin production. T1DM is associated with various other autoimmune disorders, including autoimmune thyroid disease, Celiac disease, and Addison disease. Detection of these antibodies is crucial to prevent morbidity related to unrecognized disease. Indian data regarding prevalence of these antibodies in T1DM is lacking, particularly antibodies against 21 hydroxylase. Patients and Methods: Total 100 patients with T1DM were taken into the study, in all patients anti-transglutaminase (anti-tTG) IgA, anti-thyroid peroxidase (anti-TPO) were done, and 21 hydroxylase anti bodies were done in 86 cases. Descriptive statistics were reported using mean, SD, numbers, and percentages. Student's t-test was used to assess the differences between the groups. Results: Fifteen cases were found to be TPOAb positive (eight had hypothyroidism, two had sub-clinical hypothyroidism, and five cases had normal thyroid function). tTGAb were positive in four cases, three were positive for 21-Hyroxylase antibody, and all had normal cortisol levels. Conclusion: Organ-specific autoimmune antibodies were elevated in T1DM when compared to general population. Screening of all these antibodies in T1DM patient should become standard of care.

The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.

Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23–15.39) for AGA IgA and 3.08 (95% CI 1.19–7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.

Positive tissue transglutaminase antibodies with negative endomysial antibodies: Unresolved issues in diagnosing celiac disease

BackgroundThe serological screening for celiac disease (CD) is currently based on the detection of anti-transglutaminase (tTG) IgA antibodies, subsequently confirmed by positive endomysial antibodies (EMA). When an anti-tTG IgA positive/EMA IgA negative result occurs, it can be due either to the lower sensitivity of the EMA test or to the lower specificity of the anti-tTG test. This study aimed at verifying how variation in analytical specificity among different anti-tTG methods could account for this discrepancy. MethodsA total of 130 consecutive anti-tTG IgA positive/EMA negative samples were collected from the local screening routine and tested using five anti-tTG IgA commercial assays: two chemiluminescence methods, one fluoroimmunoenzymatic method, one immunoenzymatic method and one multiplex flow immunoassay method. ResultsTwenty three/130 (17.7%) patients were diagnosed with CD. In the other 107 cases a diagnosis of CD was not confirmed. The overall agreement among the five anti-tTG methods ranged from 28.5% to 77.7%. CD condition was more likely linked to the positivity of more than one anti-tTG IgA assay (monopositive = 2.5%, positive with ≥ three methods = 29.5%; p = 0.0004), but it was not related to anti-tTG IgA antibody levels (either positive or borderline; p = 0.5). ConclusionsPatients with positive anti-tTG/negative EMA have a low probability of being affected by CD. Given the high variability among methods to measure anti-tTG IgA antibodies, anti-tTG-positive/EMA-negative result must be considered with extreme caution. It is advisable that the laboratory report comments on any discordant results, suggesting to consider the data in the proper clinical context and to refer the patient to a CD reference center for prolonged follow up.