SEQUENTIAL ANALYSIS OF HLA-CLASS II ANTIGEN EXPRESSION IN HUMAN RENAL ALLOGRAFTS Induction of Tubular class II Antigens and Correlation with Clinical Parameters

Abstract

The expression of HLa-class II antigens was assessed in 142 biopsies from 29 recipients of cadaveric renal alllografts who received either short-term cyclosporine (N=12) or azathioprine and low-dose prednisolone (n=17). Biopsies were obtained before transplantation, routinely at days 7, 21, 90, and 365 after transplantatioin, and at other times as clinically indicated. Cryostat sections were labeled with monoclonal antibodies using an indirect immunoperoxidase technique. In all biopsies HLA-class II antigens were expressed on glomeruli and intertuvular structures. In pretransplant biopsies poroximal tubules expressed class II antigens, whereas distal tubules were always negative. After transplantation three patterns of class II expression were recognized based on renal tubular class II staining: normal, focal increased, and generalized increased expression. Sequential biopsy analysis showed fluctuating levels of expression in individual patients, which correlated with cellular infiltration and was associated with allograft rejection. 71% of biopsies obtained at day 90 from patients on conventional therapy showed increased class II expression compared with only 9% of biopsies from patients on cyclosporine immunosuppression. All patients with normal class II antigen expression in day 90 biopsies had well-functioning grafts two years after transplantation, whereas 3 of 9 with increased class II antigen expression had failed. Furthermore, all grafts failing from irreversible rejection before 90 days showed marked increase of class II antigen expression. The increased class II antigen expression in renal allografts may be merely a marker of rejection or may have a role in the augmentation of the response, either in its induction or as a target for the effector arm of the reaction.