Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides

Abstract

Objective. To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN).Methods. Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibodypositive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining).Results. In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class I11 and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expres- Submitted for publication June 3, 1996; accepted in revised form July 17, 1996. sion was similarly observed in other inflammatory renal diseases.Conclusion. This study shows that CD40 is expressed on a variety of renal parenchymal and nonparenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class I11 and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

Human Platelets Stimulate Mesangial Cells to Produce Monocyte Chemoattractant Protein-1 via the CD40/CD40 Ligand Pathway and May Amplify Glomerular Injury

“…Our data suggest that the protective effect of anti-CD40L in this disease may partly reflect inhibition of MCP-1 production after platelet/MC interactions. CD40L-positive leukocytes are rarely observed in glomeruli as compared with the interstitium in proliferative lupus nephritis (16), further strengthening the idea that plateletbound CD40L might be the predominant ligand source for CD40 on MC. A functional soluble form of CD40L has recently been reported (39,40), suggesting that platelets may stimulate MC through either soluble or cell-surface CD40L.…”

“…Platelets were cocultured with MC at the ratio of 1:100 in the presence or absence of antibodies for 24 h. Inhibition of CD40/CD40L reduced MCP-1 induction by approximately 60%, whereas blocking of P-selectin or ␤1-integrins did not significantly affect the results (Figure 4). Although immunohistochemical analysis has shown that CD40 is expressed on MC in renal biopsy from patients with a variety of glomerulonephritides (16), its expression on cultured MC has not been identified. Therefore we examined CD40 expression on MC by FACS analysis, and we found that MC constitutively expressed CD40 ( Figure 5).…”

“…CD40 is also found on monocytes, macrophages, and endothelial cells, suggesting that CD40L has a broader immunologic function in vivo (15). Upregulation of CD40 on MC has been observed in renal biopsies of patients with inflammatory glomerulonephritides such as lupus nephritis and IgA nephropathy (16). CD40/ CD40L interactions between infiltrating mononuclear cells and resident renal cells are thought to play an important role in the pathogenesis in immune-mediated glomerulonephritis (17).…”

Effects of different LDL particles on inflammatory molecules in human mesangial cells

“…Upregulation of CD40 in mesangial cells has been observed in renal biopsies of patients with inflammatory glomerulonephritides such as lupus nephritis and IgA nephropathy [17].…”

Le CD154 plaquettaire : Une nouvelle interface dans l’hémostase et la réaction inflammatoire

“…Ces données, confirmées dans d'autres modèles [41,42], ont suggéré que les conséquences bénéfiques, sur la glomérulo-pathie, de la neutralisation du CD154 étaient en rapport avec un effet local, indépendant de l'inhibition de la production des auto-anticorps pathogènes, d'autant qu'il existe une augmentation importante de l'expression du CD40 glomérulaire dans la néphropathie lupique [43]. Des données expérimentales appuient cette hypothèse, puisque le CD154 des plaquettes de patients présentant un LED (lupus étythéma-teux disséminé) induit l'expression du CD40 sur les cellules mésangia-les, stimule leur prolifération et augmente leur production de TGF-β [44].…”