Clinical and Prognostic Characteristics of "Disease-specific" Autoantibodies in Systemic Scleroderma

Abstract

Systemic sclerosis (SSc) is a connective tissue disease of autoimmune nature characterized by the triad of vascular injury, autoimmunity (cellular and humoral) and tissue fibrosis. Autoantibodies do not seem to be simply epiphenomena, but are involved in disease pathogenesis. It is believed that the SSc-specific autoantibodies are responsible both for amplifying immune response and targeting cell types that are relevant in the pathophysiology of SSc. In the current understanding of the pathogenesis of SSc, the leading role is assigned to the vascular lesion of the microvasculature arising against the background of immunity dysregulation and the intensification of fibrosis processes associated with the action of various growth factors and cytokines. In SSc, as in other systemic autoimmune diseases, chronic B-lymphocytic activation is observed, which results in a loss of tolerance to self antigens. Circulation of a wide range of autoantibodies (antibodies) is a characteristic feature of SSc. It is possible that autoantigens in SSc are released during ischemia-reperfusion tissue damage that occurs against the background of vasospastic vascular reactions characteristic of this disease. In the process of B-cell presentation of autoantigens through costimulatory surface molecules, activation of T-lymphocytes occurs, followed by clonal expansion of T-cell subpopulations, which are autoreactive towards endothelium and fibroblasts. It is believed that B cells play an important role in the initial mechanisms of fibrosis in SSc, and chronic activation of B cells is directly related to the development of sclerodermic fibrosis through the production of antibodies and fibrogenic cytokines. Despite many years of efforts, a complete concept explaining the role of antibodies in the pathogenesis of SSc has not yet been created. At the same time, a huge amount of information has been accumulated on the diagnostic and prognostic significance of circulating antibodies, the importance of which for the supervision of the patient can hardly be overestimated.