ANTIBODY-DEFINED VARIANTS OF SYSTEMIC-SCL EROSIS - CLINICAL AND IMMUNOGENETIC ASPECTS

Systemic sclerosis (scleroderma) or scleroderma overlap syndromes are clinically polymorphous disorders. The skin (scleroderma, scleredema, dermatitis, vascular lesions), the vascular system (obliterating fibro sis of the arterial intima, microvascular lesions), internal organs (l ungs, esophagus and lower gastrointestinal tract, heart, kidney), the locomotor system (joints, tendon sheats, muscles) as well as the exocr ine glands (sicca syndrome) are involved in different frequency and se verity. More than 95% of patients with systemic sclerosis have antinuc lear antibodies (ANA) in the serum, the majority (about 90%) can be at tributed to one of 8 scleroderma related autoantibody systems. These a utoantibodies are virtually exclusive to each other. Autoantibodies ag ainst DNA-topoisomerase I (Scl-70), centromer antigens (CenP-A, CenP-B , CenP-C), RNA-polymerase I, II or III, Th-(To-)RNP or fibrillarin (U3 -RNP) are serological markers of systemic sclerosis, whereas antibodie s against U1-nRNP, PM-Scl or Ku are more frequently found in patients with scleroderma and overlapping features of other systemic connective tissue disorders like lupus erythematosus or poly-/dermatomyositis. B ased on data from the literature and our own results we will demonstra te, that patients with different scleroderma-related autoantibodies di ffer with respect to the type, frequency and severity of their clinica l manifestations and with regard to their survival rate. Renal manifes tations (renal crisis) are associated with more extensive scleroderma and antibodies to DNA-topoisomerase I or RNA-polymerases. The present data support the notion to classify systemic sclerosis or scleroderma- overlap syndromes on the basis of different autoantibodies. The strong association of different scleroderma-related autoantibodies with diff erent MHC class II alleles suggests a key role of autoantibodies in th e pathogenesis of these disorders.