RENAL LOCALIZATION OF THE MEMBRANE ATTACK COMPLEX IN SYSTEMIC LUPUS ERYTHEMATOSUS NEPHRITIS

Immune complexes localized in the kidneys of patients with systemic lupus erythematosus (SLE) 1 appear to play a central role in the pathogenesis of glomerulonephritis. Evidence supporting this hypothesis has been obtained from serial serologic studies (1-3), assay of specific antigen-antibody systems (4-7), measurement of serum immune complex levels (8-11), and immunocytochemical examination of tissues from patients with SLE (12-14). Following tissue deposition of antigen-antibody complexes, the classical complement pathway may be activated in situ, generating complement fragments and effecting the release of cellular mediators (15). Chemotaxis, vasodilation, enhanced phagocytosis, initiation of coagulation, and local tissue damage may ensue following complement activation (16). The effector mechanisms by which complement-dependent immune complexes induce injury to cells and membranes in vivo remain to be clarified. Proteolytic enzymes derived from neutrophils and serum, lymphokines, high molecular weight kininogen-kallikrein-Hageman factor coagulation pathways, and the terminal complement complex have been implicated as mediators of cytotoxicity on the basis of in vitro studies (17). To assess the role of the terminal complement complex in the inflammatory response, the tissue distribution of the membrane attack complex (MAC) comprised of C5b, C6, C7, C8, and C9, was investigated in kidneys manifesting SLE nephritis. In vitro studies have demonstrated that insertion of the MAC into the phospholipid bilayer of erythrocytes results in disruption of the membrane and cell lysis (18). In addition, the MAC has been observed on the surface membranes of neutrophils obtained from patients with SLE (19), although the pathogenetic significance of this phenomenon has not been determined. In this study the MAC was demonstrated in both glomeruli and in the region of peritubular basement membranes of kidneys with morphologic evidence of SLE nephritis. These findings suggest that the MAC interacts with sites on renal basement membranes and functions in vivo as a direct mediator of nephrotoxicity.