Related Experiment Videos
Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides
M J Yellin1, V D'Agati, G Parkinson
1Columbia University, Division of Rheumatology, New York, NY 10032, USA.
Insights
CD40 expression increases in lupus nephritis, particularly in severe forms (class III/IV). This pathway, involving CD40L+ cells, is also seen in other kidney diseases.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- CD40 ligand (CD40L) signaling is implicated in autoimmune diseases.
- Understanding CD40/CD40L roles in lupus nephritis pathogenesis is crucial.
Purpose of the Study:
- Investigate CD40 and CD40L expression in lupus nephritis.
- Elucidate potential CD40L-mediated mechanisms in lupus kidney disease.
Main Methods:
- Immunohistochemistry on patient kidney biopsies.
- Examined CD40 and CD40L expression in lupus nephritis and other kidney diseases.
- Semi-quantitative scoring of staining intensity.
Main Results:
- CD40 is normally expressed on various kidney cells.
- Marked CD40 up-regulation in class III/IV lupus nephritis, including crescents and tubules.
- CD40L+ mononuclear cells found in class IV lupus nephritis.
- Similar CD40/CD40L up-regulation observed in other inflammatory renal diseases.
Conclusions:
- CD40 is expressed in normal kidneys and up-regulated in lupus nephritis (class III/IV).
- CD40 up-regulation correlates with CD40L+ cells in lupus nephritis.
- The CD40/CD40L pathway is involved in lupus nephritis and other inflammatory kidney diseases.
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 antibody-positive 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 III 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 expression was similarly observed in other inflammatory renal diseases.
Conclusion:
This study shows that CD40 is expressed on a variety of renal parenchymal and non-parenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class III and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.