Early Microbial Markers of Celiac Disease

Background and Goals: Seroreactivity against the Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) has been detected in celiac disease patients with small-bowel mucosal atrophy. Levels of these antibodies decrease during a gluten-free diet, but their functions and time of appearance in celiac disease are not known. We aimed to search for evidence of possible microbial targets of the immune responses in the early-stage celiac disease patients who showed normal small-bowel mucosal architecture at the time of the first investigations, but later on a gluten-containing diet developed mucosal atrophy. Materials and Methods: Forty-four cases with proven early-stage celiac disease and normal mucosal morphology were enrolled. Patients' sera were tested for celiac disease antibodies against tissue transglutaminase (tTG-ab), endomysium, and for microbial antibodies against I2, OmpW, and ASCA IgG and IgA isotypes in both at the time of diagnosis and while on a gluten-free diet. Results: Thirty-four (77%) of 44 patients with early-stage celiac disease had elevated serum antibodies to one or more of the antibodies ASCA, I2, and OmpW. Furthermore, 5 of 6 cases negative for both tTG-ab and endomysium showed positivity for the microbial markers. Seroreactivity to ASCA IgA, ASCA IgG, and OmpW decreased significantly during gluten-free diet. Conclusions: Seroreactivity to different microbial antigens is evident already in patients with early-stage celiac disease. ASCA antibodies seem to be gluten-dependent. The results indicate that the microbial targets might have a role in the early development of celiac disease.