Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy

IgA nephropathy (IgAN) is the most common form of human glomerulonephritis. Tubulointerstitial inflammation with infiltration of mononuclear cells plays an important role in the progression of IgAN. Activation of T cells requires costimulatory signals through binding of CD28 receptor with cognate ligands (CD80/CD86) located on antigen-presenting cells (APC). To assess the clinical significance of this regulatory pathway participation in the pathogenesis of IgAN, a comprehensive immunohistologic evaluation was conducted on renal tissue of IgAN in different phases of progressive injury.

Thirty-three cases of IgAN and ten cases of non-IgA mesangial proliferative glomerulonephritis (PGN) with minor tissue damage as controls were investigated. Monoclonal antibodies were used to assess the expression of CD80, CD86, CD68, CD14, CD45RO, human leukocyte antigen-DR (HLA-DR), and intercellular adhesion molecule-1 (ICAM-1) in renal tissues. Clinical and expression data were compared at the time of renal biopsy.

CD80+ and CD86+ cells were observed more in IgAN patients with progressive renal injury than in mild cases and controls. CD80 was limited to tubular epithelial cells and was complemented by HLA-DR expression. CD86 was expressed in the glomerulus, periglomerular area, and peritubular interstitium. Activated T cells (CD45RO+), monocytes (CD14+), macrophages (CD68+), and CD86 showed similar distributions. Positive correlations were found between CD86+ cells and CD45RO, CD14, and CD68 positive cells and between CD80+ tubuli and peritubular interstitial CD45RO+ cells. The number of interstitial CD86 positive cells and the percentage of CD80+ tubuli were correlated with renal function. Most CD86+ cells were monocyte/macrophages.

This study suggested that CD80 and CD86 activate T cells in IgAN, CD80/CD86 expressions correlated with renal function at the time of renal biopsy, and monocyte/macrophages and tubular epithelial cells act as APC.