[Pathophysiology of Sjögren's syndrome]

Sjögren'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 isa 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 development 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.