Anti-C1q antibodies in renal and non-renal SLE.

We read with interest the report of Marto et al on the occurrence of anti-C1q antibodies in systemic lupus erythematosus (SLE), particularly their finding of anti-C1q in 39.8% of patients with SLE without renal disease, 27.3% of whom went on to develop nephritis. We recently tested for anti-C1q antibodies using an enzyme linked immunosorbent assay (ELISA) kit (Buhlmann Laboratories, Basel) in the sera of 28 patients with SLE (median 13.2 U/l (range 0.6–1516)), 14 patients with rheumatoid arthritis (RA; 12.6 (2–119.6)), and 13 healthy control subjects (5.4 (3–137.2)). Although just over 40% of patients with SLE and RA had anti-C1q levels above the manufacturer’s cut off point for positivity, 18.2 U/l, only patients with SLE had levels over 200 U/l. While we agree with Marto’s findings of a correlation between renal disease and antiC1q positivity in patients with SLE (r=0.56, p,0.05 in our study), we also found a correlation between haematological disease and anti-C1q positivity (r=0.65, p,0.05), and particularly, a negative correlation between lymphocyte count and anti-C1q concentration (r=20.55, p.0.05). Although 11/18 patients with haematological disease also had renal disease, some of the highest concentrations of anti-C1q antibody (460 and 680 U/l) were found in patients with marked lymphopenia but no evidence of nephritis. Increased numbers of circulating apoptotic lymphocytes have been described in SLE, and linked with lymphopenia and disease activity. As Marto and colleagues argue, interference with clearance of apoptotic cells is now an attractive hypothesis for the development of autoimmunity. Interference of anti-C1q with the removal of the increased numbers of apoptotic lymphocytes in these lymphopenic patients might result in the exposure of antigenic nuclear material to the immune system, and so contribute to the development of autoantibodies. Although almost all studies on anti-C1q antibodies have been directed at lupus nephritis, a larger study might be useful in examining possible relationships with other forms of the disease, including haematological manifestations.