UNCOUPLING OF IMMUNE-COMPLEX FORMATION AND KIDNEY DAMAGE IN AUTOIMMUNE GLOMERULONEPHRITIS

The generation of autoantibody and subsequent tissue deposition of imm une complexes (IC) is thought to trigger the pathogenic consequences o f systemic autoimmune disease. Modulation of the autoantibody response disrupts pathogenesis by preventing the formation of ICs; however, un coupling IC formation from subsequent inflammatory responses seems unl ikely because of the apparent complexity of the IC-triggered inflammat ory cascade. However, the disruption of a single gene, which encodes t he gamma chain of the Fc receptor, was found to achieve this uncouplin g in a spontaneous model of lupus nephritis, the New Zealand Black/New Zealand White (NZB/NZW) mouse. Gamma chain-deficient NZB/NZW mice gen erated and deposited IC and activated complement, but were protected f rom severe nephritis, thus defining another potential pathway for ther apeutic intervention in autoimmune disease.