ABSTRACT: OBJECTIVES: Auto-antibodies against complement C1q strongly correlate with the occurrence of severe nephritis in systemic lupus erythematosus (SLE) patients. Identification of the C1q epitope(s) recognized by these auto-antibodies might lead to a better diagnostic assay and help elucidating the putative role of C1q and anti-C1q in SLE. METHOD: SLE patient derived anti-C1q Fabs were used in a micro-array based peptide scan to identify the peptide sequence recognized by anti-C1q. Anti-C1q Fab binding to the target peptide was further analyzed in real time (Biacore) and peptide-based ELISA's. RESULTS: A peptide scan of the collagen-like region of C1q identified two regions, one on the A-chain and one on the B-chain that are the target of the anti-C1q Fabs. Binding was confirmed by Biacore and showed nanomolar affinity. The A-chain derived peptide could specifically be detected in a peptide-based ELISA by SLE patients' sera. Competition experiments suggested that this peptide represents one of the major linear epitopes of C1q that is the target of anti-C1q in SLE. Serum antibodies from most SLE patients but not from healthy individuals specifically bound to this epitope. Binding to the peptide correlated with binding of the same sera to native C1q but was found to be more sensitive for the detection of lupus nephritis. CONCLUSION: We identified a major linear epitope of C1q that is the target of anti-C1q in SLE. The ELISA-based assay using this peptide was more specific and more sensitive than a conventional anti-C1q assay for the detection of SLE patients with active nephritis.
Arthritis & Rheumatism 06/2012; · 7.87 Impact Factor