Pathophysiology of Sjogren's syndrome

Sjogren's syndrome (SS) is an excellent model for understanding the pathophysiology of autoimmune diseases and the relationships between autoimmunity and lymphoma. Recently discovered new elements probably play a role in the pathogenesis of this multifactorial disease: genetic predisposition remains largely unknown, but there is a link between certain HLA molecules and the type of autoantibodies secreted; sometimes called autoimmune epithelitis, SS is associated with abnormal apoptosis activity in epithelial cells leading to an abnormal accumulation of degradation products of the cytoskeleton proteins such as alpha- and beta-fordrine and also to the presentation of numerous antinuclear autoantigens to the immune system; significant polyclonal activation of B lymphocytes is probably mediated, at least in part, by a major increase in molecules of the TNF family (e.g. BlyS or BAFF) which play an important role in the production of autoantibodies; cytokine inhibition of healthy glands or anti-muscarin receptor antibodies and abnormal function of certain water pumps such as aquaporine could explain the perturbed function of the remaining healthy glands; permanent stimulation of autoreactive B cells favors oncogenic events and could lead to the develoment of B lymphoma with autoantibody activity. The links between these different elements are progressively falling into place. A better understanding of the pathophysiology of SS can be expected to lead to the development of much needed new therapeutic tools.