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Cytokine balance in kidney tissue from lupus nephritis patients

W-S Uhm1, K Na, G-W Song

  • 1Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea.

Rheumatology (Oxford, England)
|May 6, 2003
PubMed

Insights

Interferon gamma (IFN-gamma) up-regulates CD40 in lupus nephritis, indicating a role in proliferative glomerulonephritis. This cellular immune response activation differs between lupus nephritis WHO classes IV and V.

Area of Science:

  • Immunology
  • Nephrology
  • Cell Biology

Background:

  • Lupus nephritis is a severe complication of systemic lupus erythematosus.
  • Understanding the Th1/Th2 cytokine balance is crucial for lupus nephritis pathogenesis.
  • CD40 molecule expression is implicated in immune responses.

Purpose of the Study:

  • To determine the Th1/Th2 cytokine balance in kidney tissue of lupus nephritis patients.
  • To compare cytokine balance between lupus nephritis WHO classes IV and V.
  • To investigate the role of CD40 in lupus nephritis.

Main Methods:

  • Flow cytometry assessed CD40 expression on human mesangial cells stimulated with IFN-gamma, IL-4, and IL-10.
  • Kidney tissue sections from lupus nephritis and minimal-change disease patients were stained for various immune markers (IL-4, IL-10, IL-12, IFN-gamma, CD4, CD8, CD40, CD68, CD40L).

Main Results:

  • IFN-gamma up-regulated CD40 on mesangial cells; Th2 cytokines (IL-4, IL-10) did not down-regulate it.
  • Glomeruli showed significantly higher CD40 expression and IFN-gamma/IL-10, IL-12/IL-4, and (IFN-gamma+IL-12)/(IL-4+IL-10) ratios in class IV vs. class V lupus nephritis.
  • CD40, IFN-gamma, and renal biopsy activity index were closely correlated.

Conclusions:

  • IFN-gamma may drive proliferative glomerulonephritis by up-regulating CD40.
  • This suggests IFN-gamma activates the cellular immune response in human lupus nephritis.
  • The findings highlight differences in cytokine balance between lupus nephritis classes IV and V.
Abstract

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