Complement membrane attack (MAC) in idiopathic IgA-glomerulonephritis

Abstract

Antigens of the membrane attack complex of complement (MAC), such as C5, C6, C9 and MAC-related neoantigen(s), were demonstrated in the mesangium of 23 cases with IgA-glomerulonephritis (IgA-GN) and two cases with Henoch-Schonlein purpura nephritis (HSP). High specificity of the polyclonal antibodies was verified by dot-blot analysis. Control specimens lacking immunoglobulin deposits were negative for MAC-related antigens. Markers of classical pathway activation (C1q and C4) were observed only in two of 24 and one of 23 cases of IgA-GN and HSP, respectively. Glomerular distribution patterns (mesangial vs. mesangio-peripheral) of immunoglobulin or complement deposits were correlated for IgA and C3b/iC3b ((P<0.002), for IgA and properdin (P<0.002) and for IgA and MAC neoantigens (P<0.01). Double immunostaining experiments revealed co-localization of IgA and MAC neoantigens at identical mesangial and capillary sites. Glomerular distribution of the less pronounced IgG or IgM deposits did not correlate with that of any complement-derived antigen. The pattern of MAC-related antigens was found to be uniformly either mesangial or mesangio-peripheral. Staining for MAC-related antigens was less intense in IgA-GN cases with minimal glomerular lesions than in cases with more advanced non-sclerosing lesions. IgA, C3d, and MAc localized in corresponding glomerular sites. This is consistent with complete local activation of complement by glomerular IgA deposits via the alternative pathway. The possibility exists that MAC plays a pathogenetic role, such as by irritation of bystander cells, in IGA-GN and HSP.