Anti-transglutaminase antibodies in non-coeliac children suffering from infectious diseases

Abstract

SummaryAnti-transglutaminase antibodies are the diagnostic markers of coeliac disease. A role is suggested for infectious agents in the production of antitransglutaminase antibodies. The aim was to measure positive antitransglutaminase antibody levels in children with infectious diseases and to compare immunological and biological characteristics of the antitransglutaminase antibodies derived from these children with that from coeliac patients. Two hundred and twenty-two children suffering from infectious diseases were enrolled prospectively along with seven biopsy-proven coeliacs. Serum samples were tested for anti-transglutaminase antibodies and anti-endomysium antibodies; positive samples were tested for coeliac-related human leucocyte antigen (HLA)-DQ2/8 and anti-viral antibodies. Purified anti-transglutaminase antibodies from the two study groups were tested for urea-dependent avidity, and their ability to induce cytoskeletal rearrangement and to modulate cell-cycle in Caco-2 cells, using phalloidin staining and bromodeoxyuridine incorporation assays, respectively. Nine of 222 children (4%) tested positive to anti-transglutaminase, one of whom also tested positive for anti-endomysium antibodies. This patient was positive for HLA-DQ2 and was diagnosed as coeliac following intestinal biopsy. Of the eight remaining children, two were positive for HLA-DQ8. Levels of anti-transglutaminase returned to normal in all subjects, despite a gluten-containing diet. Purified anti-transglutaminase of the two study groups induced actin rearrangements and cell-cycle progression. During an infectious disease, antitransglutaminase antibodies can be produced temporarily and independently of gluten. The infection-triggered anti-transglutaminase antibodies have the same biological properties as that of the coeliacs, with the same in-vivo potential for damage.

Screening for celiac disease in the general population and in high‐risk groups

“…The introduction of endomysium antibodies was initially promising, because their sensitivity and specificity seemed to be at least 90-95%; but over time, issues regarding inter-observer reliance/interpretability and cost, have limited its use as the first-line screening tool for CD. Though TTG antibodies can also be elevated in non-CD diseases such as liver disease, 26 gastrointestinal infections 27 and certain heart diseases; 28,29 TTG, like EMA, offers high sensitivity and specificity. 30 One further test recently gained some popularity: This is for deamidated gliadin peptide antibodies (DGP); however, one meta-analysis found that TTG performs better than DGP.…”

Immunological Approach of the Challenges of the XXI Century in Celiac Disease

“…The CD-specific autoantibodies targeted against TG2 cause disorganization of the actin cytoskeleton [36]. Purified TG2 induced actin rearrangements and cell-cycle progression [37]. The disappearance of IgA antimicrofilament after gluten withdrawal predicted the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe CD [38].…”

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

“…The AEA was determined using human umbilical cord sections as previously reported. 4 Serum IgA anti-TG, and organ-specific auto-antibodies (thyroperoxidase antibodies, glutamic acid decarboxylase autoantibodies, islet-antigen 2 antibodies) were all measured following the manufacturer's instructions (Eurospital, Trieste, Italy). Serum auto-antibodies were evaluated in our 2 cases and in patients highly suspected for celiac disease at diagnosis and on 3 more occasions during follow-up.…”

“…3 Anti-TG were identified during infections in 4% of infected children, whether they were celiac disease-related HLA carriers or not, and later disappeared on a normal diet. 4 We report 2 children with upper airway infection found to have a high serum concentration of anti-TG that did not originate in the intestine and were not related to gluten ingestion. Both were tested to measure the most common serum glutendependent organ-specific antibodies found in some patients with untreated celiac disease.…”