Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis

Abstract

Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.