PoM No 3, 2014

Publication of the Month


March 03/14: Microbial involvement in Celiac Disease pathogenesis


Key messages:

  • Most CD patients show seroreactivity to specific microbial antigens very early in the disease process – even before mucosal damage is evident.
  • Bacterial flora may play a role in the pathogenesis of CD and offer new possibilities for research


Viitasalo L, Niemi L, Ashorn M, Ashorn MS, Braun J, Huhtala H, Collin P, Mäki M, Kaukinen K, Kurppa K, Itanen S
Early Microbial Markers of Celiac Disease
J Clin Gastroenterol 2014; doi: 10.1097/MCG.0000000000000089


Background: The structural damage which is diagnostic of celiac disease (CD) is only the final outcome of a gradually developing inflammatory process. Recent studies have suggested a role of enteric microbiota in the pathogenesis of celiac disease. Antibodies against Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescence-associated sequence (I2) and Bacteroides caccae Ton-B-linked outer membrane protein (OmpW) can be detected in overt CD and titers of these microbial seromarkers may decrease with a gluten-free diet. These authors aimed to investigate antibodies to these microbial antigens in the early stage of CD when the small-bowel mucosa is still normal.


Summary: This study looked at 44 CD patients who were initially suspected of CD but who had normal ileal mucosal villous structure (Marsh I or II) when biopsied. Some of these patients went on to develop Marsh III CD while others were not followed histologically but all expressed DQ2 or DQ8 HLA type and responded beneficially to a gluten-free diet. Sera were available from all patients at varying times in their diagnosis, treatment and follow-up. 38 (86%) of the 44 patients expressed positive serum tTG-ab and/or EMA. At baseline, 34 (77%) patients had positive seroreactivity to one or more of the studies microbial antigens. Significant decrease was seen in ASCA and I2 titers during the 1-year, gluten-free follow-up.


Conclusions: This study shows for the first time that a serological response to defined microbial antigens can be detected in the early stages of CD when the mucosal villi are still morphologically normal. It also shows that such seropositivity can be present in the absence of the traditional CD antibodies (tTG and EMA).


Comment: The results of this study suggest that intestinal bacterial flora may play a role in the pathogenesis of CD. The early appearance and gluten sensitivity of the microbial seromarkers may offer new tools for the diagnosis and follow-up of autoantibody-negative CD. In any case, the study opens new possibilities for determining the origins and disease course of CD and assisting in the path towards further understanding and ultimately better patient care for these patients 


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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.