Systemic Sclerosis: New Insights in Autoimmunity (44424)

Abstract

The strong female predilection of systemic sclerosis, especially in women after their childbearing years, and the clinical and histopathological similarities with chronic graft-versus-host disease make systemic sclerosis an interesting subject of debate. Recent studies concerning the pathogenesis of this disease demonstrated the persistence of fetal cells in the maternal circulation in a majority of female patients. How or whether microchimerism is involved in the pathogenesis of systemic sclerosis remains to be elucidated. The present paper reviews the recent findings on the subject. (P.S.E.B.M. 1999, Vol 222) Systemic sclerosis (SSc) is a connective tissue disease characterized by three features: 1) induration and thickening of the skin due to excessive collagen deposition; 2) abnor- malities involving both the microvasculature and larger ves- sels (e.g., Raynaud's phenomenon); and 3) fibrotic degen- erative changes in muscles, joints, and internal organs like the esophagus, intestinal tract, heart, lungs, and kidneys (Table I) (1-3). SSc has been described in all races and is global in its distribution. The incidence of SSc is approxi- mately between 4 and 12 individuals per million per year. The 5-year cumulative survival rate is around 50%. The disease is three to eight times more common in women than men, and its onset is the highest in the fourth and fifth decades of life (4-8). SSc is characterized by the presence of autoantibodies (i.e., antinuclear antibodies, ANA). Antibodies virtually specific for SSc include antibodies to topoisomerase I (ScL- 70), a nonhistone nuclear protein, and anticentromere anti- bodies (1). Results of recent studies suggest that SSc is a disease of major histocompatibility complex (MHC)- associated autoantibody responses. Both the anticentromere and the antitopoisomerase I antibody responses have been linked to HLA-DQB1 alleles, although recent data suggest that certain HLA-DRB1 alleles are important for the anti- topoisomerase I response and that HLA-DPB1 alleles may also have a role (9). It was proposed by Arnett (10) that certain HLA class II alleles, especially HLA-DQ, are more strongly associated with autoantibody subsets of SSc than with the disease itself. He showed, for example, that anti- centromere antibodies are strongly associated with HLA- DQB1*0501 (DQ5) and DQB1*0301 (DQ7) alleles and that antitopoisomerase I antibodies occur in SSc patients with HLA-DQB1*0301 (DQ7), DQB1*0302 (DQ8), and DQB1*0601 (DQ6) alleles.