69 - Nephritic factor autoantibodies

Abstract

Data accumulated over the past 25 years strongly suggest that C3 nephritic factor (C3NeF) is a typical antibody. Germline genes are involved in the production of C3NeF and the ability to make C3NeF is apparently present in everyone from the time of birth. Because the autoantigen of C3NeF is present in early fetal life and because C3 and Factor B interact continuously in the circulation to generate C3 convertase (C3bBb), it is possible that this constant antigenic stimulus gives rise to clones of cells producing C3NeF, which are specific and of high affinity. Patients with membranoproliferative glomerulonephritis (MPGN) should be screened for C3NeF and its presence should be verified by tests involving the stabilization of the C3bBb on the surface membrane of red blood cells. If not detected, the possibility of the presence of anti-Factor H antibodies or Factor H mutations should be considered. The fact that dense deposits appear on renal allografts suggests that C3NeF can cause renal pathology by activating complement. B cell depletion and complement activation inhibition remain to be evaluated as possible therapeutic tools. The method for detecting C3NeF relies on precipitation of IgG from the patient's serum and addition of that IgG fraction to sheep cells bearing C3bBb (EC3bBb). Decay dissociation of EC3bBb (which can be made in several different ways) is prevented by C3NeF.