Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry¹

Nature Medicine,11, 85-89, 2005

Speaker: 劉倩如                              Time: 02/23/2005 14:00~15:00

Commentator: 林秋烽博士                      Place: 601教室

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the production of a wide spectrum autoantibodies directed against nuclear, cytoplasmic, and cell membrane autoantigens.²The etiology of SLE is not completely understood to date. According to many previous studies, Epstein-Barr virus (EBV) has been found to play a critical role in the pathogenesis of SLE. Antibodies to Ro protein are common in SLE and are, on average, the earliest autoantibodies detected in the preclinical period, as individuals progress toward clinical SLE. In this study, the author first uses 531 overlapping octapeptides of Ro protein to screen specific epitope that was recognized by autoantibodies of SLE patients. Among which, Ro_169-180 peptide was identified to be the initial epitope. In addition, Ro_169-180 antibodies were demonstrated to cross react with EBNA-1_58-72. Ro peptide-immunized animals develop cross-reactive autoimmunity against EBNA-1. Finally, rabbits immunized with EBNA-1_58-72 peptide could result in epitope spreading and human lupus-like autoimmunity against Ro protein. In conclusion, these data presented herein strongly support virus-induced molecular mimicry originating from EBV may act as an etiologic role for the pathogenesis of SLE.

Reference

1. McClain, M. T. et al. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med 11, 85-9 (2005).

2. Riemekasten, G. et al. A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus. J Clin Invest 102, 754-63 (1998).