Complement and arthritis: another step in understanding

Michael M Frank, C Garren Hester

In a recent research article in Arthritis Research and Therapy ('Analysis of C204 and the C4 binding protein in the MRL/lpr mouse'), Wenderfer and colleagues report that deficiency in C4 binding protein, a down-regulator of the classic pathway of complement, does not affect the development of autoimmune disease. These data support the earlier finding that the alternative pathway, and not the classic pathway, drives disease progression. However, in a milder variant of the MRL/lpr model, the lpr/lpr mouse, classic pathway deficiency does contribute toward renal pathology and more severe disease. In this editorial we discuss the factors that may cause such a discrepancy.