Apoptosis and peripheral blood lymphocyte depletion in coeliac disease

In coeliac disease (CD) immunological abnormalities are not confined to the small bowel and it has been suggested that changes in peripheral blood lym phocytes (PBL), such as lymphopenia and increased T-cell activation, may pr edispose to malignant or autoimmune complications of this condition. In the light of the recent findings about the Fas-Fas ligand (FasL) system in reg ulating lymphocyte homeostasis, the aim of the present study was to investi gate peripheral lymphocyte Fas-mediated apoptosis in CD to establish whethe r the homeostatic role of apoptosis in peripheral T-cell selection is maint ained. Moreover, because a soluble form of Fas has been described to be fun ctionally implicated in the Fas signalling system, suggesting a relationshi p between some disorders and soluble Fas function, we measured levels of so luble Fas in sera of coeliac patients and analysed the relationship between these levels and the proportions of apoptotic and Fas(+) PBL to further ex plore the function of the Fas-FasL pathway in this condition. Finally, we e valuated whether the increased prevalence of anticardiolipin antibodies, re cently described in CD, could be related to PBL apoptosis in this condition . We demonstrated an increased apoptosis and higher levels of Fas and FasL expression in PBL isolated from untreated coeliac patients when compared to treated coeliac patients and controls. In addition, low levels of soluble Fas and a significant positive correlation between anticardiolipin antibodi es and PBL apoptosis were found in untreated CD. Then, our results showed a n increased susceptibility of PBL to undergo Fas-mediated apoptosis in acti ve CD. This increased apoptosis could be responsible for both lymphopenia a nd immunogenic exposure of phospholipids with subsequent production of auto antibodies.