Immunopathogenesis of Sjogren's syndrome: "facts and fancy"

Sjogren's syndrome (Ss) is an ideal model to study the pathogenesis of both autoimmunity and malignancy. It occurs as an organ specific autoimmune disease, alone or in association with almost every other autoimmune disorder, as a systemic disorder, and finally it can evolve to B-cell-lymphoid malignancy. The most consistent finding in the syndrome, the B-cell-hyperreactivity, follows the same steps of evolution. It starts as polyclonal, but not random, since the autoantibody profile correlates with the disease subgroups and the systemic manifestations and it seems to be controlled by the MHC gene composition. Further, in the systemic form of the disease it presents as a poly-oligo-mono-clonal process and ends up to monoclonal (IgMk) B-lymphoid malignancy. Studies on the T-immunoregulatory subsets and function can not explain this B-cell hyperreactivity. The initial trigger is unknown. Estrogens, known as immunoenhancers possibly promote the B-cell hyperreactivity and certain genes controlling HLA class-II MHC molecules may represent susceptibility factors for the development of the disease. The discovery of lymphokines and particularly the B-cell growth and differentiation factors as well as the rapid development of the retro-virology field may give answers pertinent to the pathogenesis of Ss and to B-cell lymphoid malignancy.