Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.

Abstract

The membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.

CR1 stump peptide and terminal complement complexes are found in the glomeruli of lupus nephritis patients

“…Our TCC data confirm the results obtained by Biesecker et al [27] and demonstrate different histological patterns in glomerular TCC deposits which varied with the severity of glomerular damage. Less severe glomerular lesions presented TCC deposits especially in the mesangium (mesangial pattern).…”

Induced Expression of FcγRIIIa (CD16a) on CD4+ T Cells Triggers Generation of IFN-γhigh Subset

“…Both ICs and C5b-9 are present within the immune deposit, 3 A. Chauhan, unpublished observation. which occurs in vascular sites in conditions such as lupus nephritis and arthritic synovium (50,51). Thus those naïve CD4 ϩ T-cells that will come in contact with immune deposits will trigger their differentiation into CD4 ϩ Fc␥RIIIa ϩ IFN-␥ high population resulting in high IFN-␥ in localized tissue.…”

Activated Protein C Attenuates Systemic Lupus Erythematosus and Lupus Nephritis in MRL-Fas(lpr) Mice

“…In SLE, renal damage and dysfunction result from immune complex glomerulonephritis, in which glomerular deposits of immune complexes activate the components of the classical complement pathway, which finally leads to the assembly of the C5b-9 multimer membrane attack complex (21). The favorable effects of recombinant activated protein C treatment on markers of active lupus nephritis were associated with a significant reduction of glomerular IgG deposits as well as the deposition of complement factor C3c, a marker of intraglomerular complement activation (Fig.…”