Potential Celiac Disease in Children: Health Status on A Long-Term Gluten-Containing Diet.

Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children's parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, p < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.

Prevalence and factors associated with celiac disease in high-risk patients with functional gastrointestinal disorders.

Celiac disease (CD) is an autoimmune disease of the small intestine triggered by the consumption of gluten-containing foods in individuals with a genetic predisposition. CD was a rare disease until 20 years ago, when the prevalence increased. Currently, there is no data on the prevalence of CD in high-risk adult populations in Indonesia, even though there is a trend of increasing gluten consumption. Therefore, basic research is needed to determine the magnitude of CD in high-risk adult patients in Indonesia while identifying clinical signs/symptoms, illness history, and lifestyle to determine factors associated with CD in Indonesia. This study is an observational study with a cross-sectional method.Two hundred eighty-three patients who fulfilled the selection and signed the informed consent were recruited from the gastroenterology clinic of Dr. Cipto Mangunkusumo General Hospital. Patients were asked to fill out a celiac disease-related questionnaire and then given anthropometry measurement and blood test for serologic examination with ELISA, consisting of IgA anti-tissue transglutaminase (anti-TTG) and IgG anti-deaminated gliadin peptide (anti-DGP). Statistical analysis was performed using Chi-square and Multivariate logistic regression tests with SPSS software ver. 26. Statistical test differences were considered significant if the p-values were < 0.05. Eight of 283 patients are serologically confirmed with CD (2,83%). On bivariate analysis, the significant variables are age (p < 0,05), constipation (p < 0,05) and history of autoimmune disease (p < 0,05). On multivariate analysis, the only significant variable is the history of autoimmune disease (p < 0,05). This study concluded that the prevalence of CD in high-risk patients with functional gastrointestinal disorder at Dr. Cipto Mangunkusumo Hospital is relatively high (2.83%). CD-associated factors are age, constipation, and history of autoimmune disease in patients. On simultaneous interaction between these factors, autoimmune is the only significant variable associated with CD.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Outcome in pediatric celiac disease is independent of the diagnostic approach in patients with high antibody levels.

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.

Chronic diarrhoea, weight loss and a positive anti-tissue transglutaminase antibody: A case report of olmesartan-induced enteropathy.

Olmesartan is an angiotensin II receptor blocker licensed for the treatment of hypertension. It can cause a sprue-like enteropathy (SLE), characterised by chronic diarrhoea, weight loss and villous atrophy. Transiently raised anti-tissue transglutaminase (ATTG) antibody has also been rarely reported in the literature.We describe the case of a woman in her mid-50s, who presented with a history of intermittent loose stools over 1 year, associated with significant weight loss. She had two marginally raised serum ATTG antibody tests during her work-up.After extensive investigations, she was diagnosed with olmesartan-induced enteropathy. On subsequent follow-up, her symptoms had resolved with cessation of her olmesartan therapy.This case adds to existing literature, highlighting the importance of considering olmesartan as a possible differential diagnosis for SLE. It also reports the presence of a raised ATTG antibody which is infrequently reported in this context.

Selective activation of naïve B cells with unique epitope specificity shapes autoantibody formation in celiac disease.

Many antibody responses induced by infection, vaccination or autoimmunity show signs of convergence across individuals with epitope-dependent selection of particular variable region gene segments and complementarity determining region 3 properties. However, not much is known about the relationship between antigen-specific effector cells and antigen-specific precursors present in the naïve B-cell repertoire. Here, we sought to address this relationship in the context of celiac disease, where there is a stereotyped autoantibody response against the enzyme transglutaminase 2 (TG2). By generating TG2-specific monoclonal antibodies from both duodenal plasma cells and circulating naïve B cells, we demonstrate a discord between the naïve TG2-specific repertoire and the cells that are selected for autoantibody production. Hence, the naïve repertoire does not fully reflect the epitope preference and gene usage observed for memory B cells and plasma cells. Instead, distinct naïve B cells that target particular TG2 epitopes appear to be selectively activated at the expense of TG2-binding B cells targeting other epitopes.

Generation of circulating autoreactive pre-plasma cells fueled by naive B cells in celiac disease.

Autoantibodies against the enzyme transglutaminase 2 (TG2) are characteristic of celiac disease (CeD), and TG2-specific immunoglobulin (Ig) A plasma cells are abundant in gut biopsies of patients. Here, we describe the corresponding population of autoreactive B cells in blood. Circulating TG2-specific IgA cells are present in untreated patients on a gluten-containing diet but not in controls. They are clonally related to TG2-specific small intestinal plasma cells, and they express gut-homing molecules, indicating that they are plasma cell precursors. Unlike other IgA-switched cells, the TG2-specific cells are negative for CD27, placing them in the double-negative (IgD-CD27-) category. They have a plasmablast or activated memory B cell phenotype, and they harbor fewer variable region mutations than other IgA cells. Based on their similarity to naive B cells, we propose that autoreactive IgA cells in CeD are generated mainly through chronic recruitment of naive B cells via an extrafollicular response involving gluten-specific CD4+ T cells.

Potential therapeutic options for celiac Disease: An update on Current evidence from Gluten-Free diet to cell therapy.

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment.

Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease.

BACKGROUND & AIMS: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment. METHODS: We followed 17 CeD patients during their initial GFD year, leading to disease remission. We assessed activation and frequency of gluten-specific CD4+ blood and gut T cells with HLA-DQ2.5:gluten tetramers and flow cytometry, disease-specific serology, histology, and symptom scores. We assessed gluten-specific blood T cells within the first 3 weeks of GFD in 6 patients and serology in an additional 9 patients. RESULTS: Gluten-specific CD4+ T cells peaked in blood at day 14 while up-regulating Bcl-2 and down-regulating Ki-67 and then decreased in frequency within 10 weeks of GFD. CD38, ICOS, HLA-DR, and Ki-67 decreased in gluten-specific cells within 3 days. PD-1, CD39, and OX40 expression persisted even after 12 months. IgA-transglutaminase 2 decreased significantly within 4 weeks. CONCLUSIONS: GFD induces rapid changes in the phenotype and number of gluten-specific CD4+ blood T cells, including a peak of nonproliferating, nonapoptotic cells at day 14. Subsequent alterations in T-cell phenotype associate with the quiescent but chronic nature of treated CeD. The rapid changes affecting gluten-specific T cells and disease-specific antibodies offer opportunities for clinical trials aiming at developing nondietary treatments for patients with newly diagnosed CeD.

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Longitudinal screening of HLA-risk and HLA-nonrisk children for celiac disease to age 15 years: CiPiS study.

OBJECTIVES: Autoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)-genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years. METHODS: Included were 13,860 HLA-DQ-genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA-DQB1*02 and/or DQB1*03:02 (HLA-risk) children were compared with non-HLA-DQB1*02 and non-DQB1*03:02 (HLA-nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody-positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease. RESULTS: At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA-risk children compared with 0/2167 HLA-nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA-risk children positive for IgA-tTG and/or IgG-tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%-1.7%) HLA-risk children were diagnosed with celiac disease compared with 0/1303 HLA-nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age. CONCLUSIONS: Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.

"Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults?

BACKGROUND: Anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. AIMS: We aimed to compare the diagnostic accuracies of ELISA-based (a-tTg/DGP) and immunofluorescence-ELISA-based strategies (EMA/a-tTg) for CD diagnosis. METHODS: From November 2020 to November 2022, we undertook an observational prospective study including consecutive adult patients with suspected CD. All subjects were tested for EMA, a-tTg and DGP IgA. An ROC curve was plotted to establish the best specificity cut-off of a-tTg and DGP levels, which would predict the presence of Marsh≥2 and Marsh=3. The diagnostic accuracies of a-tTg/DG and EMA/a-tTg were compared. RESULTS: The study included 275 CD patients. Histology showed Marsh=1 in 9.9%, Marsh=2 in 4.5%, and Marsh=3 in 85.6.%. The best cut-off value of a-tTg for predicting Marsh≥2 was 42 U/mL, while the best cut-off for predicting atrophy was 68.4 U/mL. The best cut-off value of DGP for predicting Marsh≥2 was 56 U/mL, while the best cut-off for predicting atrophy was 78 U/mL. A-tTg/EMA showed 97% sensitivity and 100% specificity, whereas a-tTg/DGP showed 94% sensitivity and 100% specificity. CONCLUSION: A-tTg/DGP is accurate for CD diagnosis and could reduce costs and operator-dependency of EMA. DGP, together with a-tTg, could replace EMA in CD diagnosis.

Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

BACKGROUND: A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. METHODS: In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76 years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. RESULTS: TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). CONCLUSIONS: This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.

Diagnosis of Seronegative and Ultrashort Celiac Disease.

In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.

Peptide Centric Vß Specific Germline Contacts Shape a Specialist T Cell Response.

Certain CD8 T cell responses are particularly effective at controlling infection, as exemplified by elite control of HIV in individuals harboring HLA-B57. To understand the structural features that contribute to CD8 T cell elite control, we focused on a strongly protective CD8 T cell response directed against a parasite-derived peptide (HF10) presented by an atypical MHC-I molecule, H-2Ld. This response exhibits a focused TCR repertoire dominated by Vß2, and a representative TCR (TG6) in complex with Ld-HF10 reveals an unusual structure in which both MHC and TCR contribute extensively to peptide specificity, along with a parallel footprint of TCR on its pMHC ligand. The parallel footprint is a common feature of Vß2-containing TCRs and correlates with an unusual Vα-Vß interface, CDR loop conformations, and Vß2-specific germline contacts with peptides. Vß2 and Ld may represent "specialist" components for antigen recognition that allows for particularly strong and focused T cell responses.

HLA DQ2/DQ8 haplotypes and anti-transglutaminase antibodies as celiac disease markers in a pediatric population with type 1 diabetes mellitus.

Objective: Evaluate the celiac disease (CD) markers, within the scope of its screening, in a pediatric population with diagnosis of type 1 diabetes (T1D) at Hospital de Braga (HB) and determine the prevalence of CD in the sample. Reflect on CD screening algorithm applied in this pediatric population. Methods: Retrospective observational study with 94 patients diagnosed with T1D at age 10 years or younger, followed up at the HB Outpatient Diabetology Consultation, including those referred from other hospitals. Record of clinical information, IgA anti-transglutaminase and anti-endomysium and HLA DQ2/DQ8 haplotypes. Results: We obtained positive serological test for CD in 4 patients. This test had 100% sensitivity and specificity. The prevalence of CD was 4.3% (n = 4). Positive HLA screening in 84.6% of patients, with both sensitivity and negative predictive value of 100% and specificity of 16.67%. Diagnosis of CD was made on average 3.40 ± 3.32 years after the diagnosis of TD1. All cases of CD registered non-gastrointestinal manifestations, none had gastrointestinal symptoms. Conclusion: This study proved that there is a higher prevalence of CD in pediatric population with TD1, when compared to general population, and clarified the importance of CD screening. Furthermore, it was observed that serological screening for CD antibodies is an excellent screening test and HLA typing, although not the most suitable first line test, can be useful in excluding the possibility of patients with T1D developing CD.

Role of HLA-DQ typing and antitissue transglutaminase antibody titres in diagnosing coeliac disease among Sudanese children with type 1 diabetes mellitus.

OBJECTIVE: The aim of the study was to determine the prevalence of coeliac disease (CD) and to recognise Human leukocyte antigen (HLA)-associated hereditary susceptibility to Sudanese CD patients with type 1 diabetes mellitus (DM1). DESIGN: Antitissue transglutaminase IgA (anti-TG IgA) was measured in the serum of 373 children affected with DM1 aged 1-19-year old and in 100 serum samples from non-diabetic control children. Histological examination was performed in 19 children seropositive for anti-TG IgA (17 DMI and 2 controls). Additionally, PCR-based analysis of Major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) genotyping was implemented in three study population groups as follows: group 1 (n=25) (+ve DM1 and +ve CD), group 2 (n=63) (-ve DM1 and +ve CD) and control group 3 (n=2) (+ve CD). RESULTS: Twenty-six Sudanese children with DM1 out of 373 (6.97%) were seropositive for anti-TG IgA. Duodenal biopsy revealed Marsh 2 and 3 in 13 out of 17 (76.47%) seropositive anti-TG IgA patients with DM1. Significant association (p<0.05) was detected between the level of anti-TG IgA autoantibodies (IU/mL) and Marsh stage. HLA DQ2 and DQ8 were found in 88% (22/25) and 8% (2/25) of examined patients with CD with DM1, respectively. CONCLUSIONS: Anti-TG IgA titre of greater than 10 times upper limit of normal (≥10× ULN) can be useful for detecting CD in children with type 1 diabetes without duodenal biopsy. HLA testing in children with DM1 appears to provide little added benefit given the high prevalence (96%) of HLA DQ2/DQ8 in children with DM1.

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

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.

Antitissue transglutaminase antibodies' normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience.

INTRODUCTION: Few data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors. MATERIAL AND METHODS: We retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD. RESULTS: TGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7-12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization. CONCLUSIONS: Our population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7-12 years for a proper management and follow-up.