Are Nephritic Factors Nephritogenic?

Abstract

HE COMPLEMENT system is a complex cascade of proteins that plays a role in a number of aspects of immune function: host de­ fence against microbial infection, particularly with encapsulated bacteria; amplification of anti­ body-mediated inflammation; efficient transport and disposal of immune complexes; induction of immune responses and antigen presentation. I In health, complement activation is tightly regu­ lated; in certain pathologic states, complement components are consumed, resulting in hypo­ complementemia. Nephrologists have long rec­ ognized the association of hypocomplementemia with certain forms of chronic glomerulonephri­ tis/ particularly the histologic type known in the United States as membranoproliferative glo­ merulonephritis (MPGN) and in Europe by the synonym mesangiocapillary glomerulonephri­ tis, which has three subtypes based on the na­ ture and distribution of the glomerular immune deposits. It remains a matter of some contro­ versy, however, whether the complement activa­ tion is a cause or a consequence of the nephritis or, indeed, merely an epiphenomenon. Activation of the complement cascade can take place via two pathways, the classical and alterna­ tive pathways, and both may be activated in ne­ phritis. This activation is often associated with the presence in the circulation of fac­ tors, which interfere with the normal regulation of complement activation. Several such factors have been described,2 of which the best charac­ terized is C3 nephritic (usually referred to simply as factor [NeF]). Nephritic is an immunoglobulin G autoantibody to neoantigens formed during assembly of the alter