Abnormal synthesis of IgA in coeliac disease and related disorders.

The pathogenesis of coeliac disease (CD) is complex. One controversial aspect is the role of IgA anti-endomysial (EMA) antibodies. Despite being the most reliable marker for CD diagnosis, its role in the pathogenesis (if any) remains obscure. The paradox is reinforced by the observation that CD is more common in IgA-deficient individuals. In this review, we discuss recent data suggesting that IgA autoantibodies may be related to aspecific dysregulation of IgA. In addition, new insights have elucidated new genes involved in IgA production and linked to CD. Allelic frequency of HS1,2 enhancer which regulates Ig synthesis is altered in CD and other IgA mediated disorders. We suggest that in CD, a T-cell mediated disease, the role of IgA anti-EMA autoantibodies remains elusive and could well be merely an epiphenomenon not directly related to pathogenic mechanisms, but rather to a state of heightened immunological responsiveness in genetically predisposed individuals.