Molecular Mimicry, Altered Apoptosis, and Immunomodulation as Mechanisms of Viral Pathogenesis in Systemic Lupus Erythematosus

摘要: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease accompanied by dysfunction of T and B lymphocytes autoantibody production. Independent lines evidence have implicated environmental factors genetic determinants the host in causation (1). Cognate T-B recognition may be necessary to produce specific autoantibodies. Helper cells from patients with active enhance production autoantibodies, whereas inactive normal do not Polymorphisms HLA molecules regulating antigen presentation (2) complement deficiency states (3) been identified as inherited influencing susceptibility. However, discordance rate SLE high 70% among monozygotic twins (2), suggesting significant role for exogenous agents. Initially, findings virion-like tubuloreticular structures endothelial well demonstration elevated serum levels type I interferon raised possibility viral etiology (4). Retroviruses were detection retroviral p30 Gag protein renal glomeruli reactivities toward (5). Indeed, many features human infections caused HTLV-I HIV-1 resemble those SLE, proteins profound effects on both effector functions immune system. Dysregulation programmed cell death (PCD) has documented HIV-infected (6) (7). Similar anemia (8), leukopenia (9), thrombocytopenia (10), polymyositis (11), vasculitis widely reported AIDS (12). Direct virus isolation transmission attempts tissues successful (13). Nevertheless, it possible that (retro)virus, responsible provoking an response crossreactive self antigens, cleared host; hence, absence particles conclusive. An alternative etiology, i.e., activation endogenous sequences (ERSs), was initially proposed study New Zealand mouse model (14). Endogenous envelope glycoprotein, gp70, found immune-complex deposits autoimmune lupus-prone NZB/NZW mice Abnormal expression ERS noted thymus strains (15,16). More recently, autoantigenicity demonstrated (17–21).