Cross-sectional study of coeliac autoimmunity in a population of Vietnamese children

Objective: The prevalence of coeliac disease (CD) inVietnam is unknown. To fill this void, we assessed the prevalence of serological markers of CD autoimmunity in a population of children in Hanoi. Setting: The outpatient blood drawing laboratory of the largest paediatric hospital in North Vietnam was used for the study, which was part of an international project of collaboration between Italy and Vietnam. Participants: Children having blood drawn for any reason were included. Exclusion criteria were age younger than 2 years, acquired or congenital immune deficiency and inadequate sample. A total of 1961 children (96%) were enrolled (838 females, 1123 males, median age 5.3 years). Outcomes: Primary outcome was the prevalence of positive autoimmunity to both IgA antitransglutaminase antibodies (anti-tTG) assessed with an ELISA test and antiendomysial antibodies (EMA). Secondary outcome was the prevalence of CD predisposing human leucocyte antigens (HLA) (HLA DQ2/8) in the positive children and in a random group of samples negative for IgA anti-tTG. Results: The IgA anti-tTG test was positive in 21/1961 (1%; 95% CI 0.61% to 1.53%); however, EMA antibodies were negative in all. HLA DQ2/8 was present in 7/21 (33%; 95% CI 14.5% to 56.9%) of the anti-tTG-positive children and in 72/275 (26%; 95% CI 21% to 32%) of those who were negative. Conclusions: Coeliac autoimmunity is rare in Vietnam, although prevalence of HLA DQ2/8 is similar to that of other countries. We hypothesise that the scarce exposure to gluten could be responsible for these findings

A Functional Idiotype/Anti-Idiotype Network Is Active in Genetically Gluten-Intolerant Individuals Negative for Both Celiac Disease-Related Intestinal Damage and Serum Autoantibodies

An unbalance between Abs that recognize an autoantigen (idiotypes; IDs) and Igs that bind such Abs (anti-IDs) is considered a functional event in autoimmune disorders. We investigated the presence of an ID/anti-ID network in celiac disease (CD), a condition in which antitissue transglutaminase 2 (TG2) Abs are suspected to contribute to CD pathogenesis. To characterize the ID side, we reproduced by in vitro yeast display the intestine-resident Abs from CD and control patients. These TG2-specific IDs were used to identify potential anti-IDs in the serum. We observed elevated titers of anti-IDs in asymptomatic patients with predisposition to CD and demonstrated that anti-ID depletion from the serum restores a detectable humoral response against TG2. Our study provides an alternative approach to quantify CD-related autoantibodies in cases that would be defined "negative serology" with current diagnostic applications. Therefore, we suggest that developments of this technology could be designed for perspective routine tests

Serum Anti-Tissue Transglutaminase Antibodies Detected during Febrile Illness May Not Be Produced by the Intestinal Mucosa

Anti-transglutaminase antibodies are the diagnostic marker of celiac disease, and are considered to be synthesized only by intestinal B-lymphocytes. During an infectious disease, these antibodies are transiently detected in serum. We show that these infection-triggered antibodies may not originate in the intestinal mucosa and are not an indication of celiac disease

Re-Discovery of Giardiavirus: Genomic and Functional Analysis of Viruses from Giardia duodenalis Isolates

Giardiasis, caused by the protozoan parasite Giardia duodenalis, is an intestinal diarrheal disease affecting almost one billion people worldwide. A small endosymbiotic dsRNA viruses, G. lamblia virus (GLV), genus Giardiavirus, family Totiviridae, might inhabit human and animal isolates of G. duodenalis. Three GLV genomes have been sequenced so far, and only one was intensively studied; moreover, a positive correlation between GLV and parasite virulence is yet to be proved. To understand the biological significance of GLV infection in Giardia, the characterization of several GLV strains from naturally infected G. duodenalis isolates is necessary. Here we report high-throughput sequencing of four GLVs strains, from Giardia isolates of human and animal origin. We also report on a new, unclassified viral sequence (designed GdRV-2), unrelated to Giardiavirus, encoding and expressing for a single large protein with an RdRp domain homologous to Totiviridae and Botybirnaviridae. The result of our sequencing and proteomic analyses challenge the current knowledge on GLV and strongly suggest that viral capsid protein translation unusually starts with a proline and that translation of the RNA-dependent RNA polymerase (RdRp) occurs via a +1/−2 ribosomal frameshift mechanism. Nucleotide polymorphism, confirmed by mass-spectrometry analysis, was also observed among and between GLV strains. Phylogenetic analysis indicated the occurrence of at least two GLV subtypes which display different phenotypes and transmissibility in experimental infections of a GLV naïve Giardia isolate

Anti-transglutaminase 6 antibody development in children with celiac disease correlates with duration of gluten exposure

Objectives: Antibodies against transglutaminase 6 (anti-TG6) have been implicated in neurological manifestations in adult patients with genetic gluten intolerance, and it is unclear whether autoimmunity to TG6 develops following prolonged gluten exposure. We measured the anti-TG6 in children with celiac disease (CD) at the diagnosis time to establish a correlation between these autoantibodies and the duration of gluten exposure. We investigated a correlation between anti-TG6 and the presence of neurological disorders. Methods: Anti-TG6 (IgA/IgG) were measured by ELISA in sera of children with biopsy-proven CD and of children experiencing gastrointestinal disorders. CD patients positive for anti-TG6 were retested after 2 years of gluten-free diet (GFD). Results: We analyzed the sera of 274 CD children and of 121 controls. Anti-TG6 were detected in 68/274 (25%) CD patients and in 19/121 (16%) controls, with significant difference between the 2 groups (P\ubc0.04). None of the CD patients and of the controls testing positive for anti-TG6 were experiencing neurological disorders. Eleven of 18 (61%) CD patients with other autoimmune diseases were positive for anti-TG6. In CD patients, a significant correlation between the gluten exposure before the CD diagnosis and anti-TG6 concentration was found (P\ubc0.006 for IgA; P<0.0001 for IgG). After GFD anti-TG6 concentrations were significantly reduced (P<0.001). No significant correlation was observed between anti-TG6 and anti-TG2 serum concentrations. Conclusions: Anti-TG6 are more prevalent in children with untreated CD in the absence of overt neurological disorders. The synthesis of the anti-TG6 is related to a longer exposure to gluten before the CD diagnosis, and the autoimmunity against TG6 is gluten dependent and disappeared during GFD

Immunohistologic analysis of the duodenal bulb: a new method for celiac disease diagnosis in children

Background and Aims: Anti-tissue transglutaminase antibodies (anti-tTG) have simplified celiac disease (CD) diagnosis. However, in atypical forms of CD, intestinal biopsy sampling is still required. This prospective study investigates whether histologic analysis of the duodenal bulb combined with intestinal IgA anti-tTG deposit immunoassay makes CD diagnosis possible in at-risk children with low concentrations of serum anti-tTG. Methods: Histologic and intestinal IgA anti-tTG deposit immunoassays were used. Results: Two hundred forty-five symptomatic children positive for serum anti-tTG (>7 U/mL) were enrolled and divided into 3 groups: extensive duodenal atrophy (n Z 209), with IgA anti-tTG deposits throughout the duodenum and high serum anti-tTG concentrations (157 178 U/mL); bulb duodenal atrophy (n Z 22), with widespread IgA anti-tTG deposits in 9 and in the bulb alone in 13 and low serum anti-tTG concentrations (13.9 8.7 U/mL); and normal duodenum (n Z 14), with widespread IgA anti-tTG deposits in 8 and in the bulb alone in 6 and low serum anti-tTG concentrations (10.6 6.2 U/mL). All patients in the first 2 groups were diagnosed with CD and 8 from the third group. All improved after 1 year of gluten-free diet. Bulb duodenal analysis led to a 12% (30/245) increase in CD diagnosis. No CD-related lesions were observed in the 30 control subjects. Conclusions: In children at risk for CD, bulb duodenum biopsy sampling is essential to identify villous atrophy and detect IgA anti-tTG deposits even in absence of intestinal lesions. These mucosal autoantibodies could well represent a new standard for diagnosing CD. (Gastrointest Endosc 2018;-:1-6.

Intestinal-mucosa anti-transglutaminase antibody assays to test for genetic gluten intolerance

Celiac disease (CD) is an autoimmune enteropathy characterized by gluten-triggered intestinal mucosa lesions in genetically susceptible individuals carrying the HLA DQ2 or DQ8. CD diagnosis is based on the concentration of IgA serum antitransglutaminase (anti-tTG) antibodies together with mucosal damage at intestinal biopsy.1 However, it is now known that in subjects with genetic gluten intolerance, gastrointestinal and extra-intestinal symptoms may be present even when both mucosal morphology and serum anti-tTGs are normal.2,3 In this context, the anti-tTG in the intestinal mucosal seem to be the specific CD immunological marker that is detectable before the development of intestinal atrophy and the appearance of serum anti-tTG.4 This prospective study investigates the presence of intestinal anti-tTG antibodies in patients with differing clinical spectrums of genetic gluten intolerance by using two immunoassays: double immunofluorescence test for anti-tTG on the intestinal mucosa and flow cytometry assay to measure acid-eluted intestinal anti-tTG