ANTIBODIES TO C1Q IN SYSTEMIC LUPUS-ERYTHEMATOSUS - CHARACTERISTICS AND RELATION TO FC-GAMMA-RIIA ALLELES

Autoantibodies to the collagen-like region of the first complement com ponent (C1qAB) are found in patients with systemic lupus erythematosus (SLE), particularly those with renal disease. In a cohort of 46 SLE p atients with diffuse proliferative glomerulonephritis, we found declin ing C1qAB titers in 77% of treatment responders and in only 38% of tre atment non-responders (P < 0.03). To further characterize this autoant ibody, we tested 240 SLE patients for the presence of C1qAB. Positive titers were found in 44% of patients with renal disease and 18% of pat ients without renal disease (X-2 P < 0.0003). Analysis of IgG subclass revealed IgG2 C1qAB alone in 34%, IgG1 C1qAB alone in 20%, and both I gG1 and IgG2 in 46% of patients. Fewer than 10% of patients had measur able titers of IgG3 or IgG4 C1qAB. The pathogenic role of these IgG2-s kewed C1qAB may relate to impaired immune complex clearance by the mon onuclear phagocyte system: IgG2 antibodies are efficiently recognized by only one IgG receptor, the H131 allele of Fc gamma RIIa (Fc gamma R IIa-H131). In contrast, Fc gamma RIIa-R131, which is characterized by minimal IgG2 binding, has recently been associated with lupus nephriti s. In our C1qAB positive patients, the presence of Fc gamma RIIA-R131 was associated with an increased risk for renal disease. Autoantibodie s to C1q may have pathogenic significance in SLE patients with genetic defects in the ability to clear IgG2 containing immune complexes.