Cutting edge: Reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide

Cyclophosphamide (CTS) prevents progression of nephritis and prolongs survi val in (NZB x NZW)F-1 (B/W) mice and is used to treat humans with lupus nep hritis, To compare the efficacy of CTLA4Ig with CTS and determine whether t here is an incremental benefit to combining CTLA4Ig with CTX, we treated B/ W mice with CTS, CTLA4Ig, or both agents. In mice with mild renal disease, treatment delayed the onset of proteinuria and prolonged survival in all gr oups, In mice with advanced renal disease, treatment with both agents reduc ed proteinuria in 71% of mice? whereas mice treated with either agent alone had no such improvement. Survival was also markedly improved among mice tr eated with both agents. Thus, combination treatment with CTX and CTLA4Ig is more effective than either agent alone in reducing renal disease and prolo nging survival of B/W mice with advanced nephritis, This striking reversal of proteinuria is unprecedented in animal models of SLE.