DETECTION OF HLA CLASS II ANTIBODIES AND THEIR RELEVANCE FOR KIDNEY GRAFT SURVIVAL.
          Schönemann C, Groth J, May G., HLA and Clinical Immunology Laboratories and Kidney Transplantation Centre, Friedrichshain Hospital, Berlin, Germany.
          Matching for the HLA class I and II antigens is known to influence the survival rate of kidney transplants. Multicenter studies demonstrate the stronger influence of HLA-DR than HLA-A and -B matching. The presence of cytotoxic anti donor HLA class I IgG antibodies (Ab) in the crossmatch (Xm) serum is a contraindication for transplantation (Tx). After Tx it is the strongest sign of vascular rejection. The clinical relevance of HLA class II Ab is less well documented mainly because their detection was difficult and laborious until now. PRA-STATâ, an ELISA for the detection of HLA class I and II Ab allows routine monitoring also for HLA-DR, and HLA-DQ Ab in a simple way. In this retrospective study, pre- and post-transplant serial sera from 50 kidney graft recipients were tested with PRA-STATâ. The results were compared with conventional complement-dependent cytotoxicity (CDC, against a 50 cell panel and donor spleen lymphocytes) and Flow cytometry (FC). Our in-house two color FC Xm allows distinction of B and T cell targets and Ig classes. Twelve of the 50 recipients underwent severe rejection episodes or graft failure in the early period after Tx. In 7 of these 12 patients HLA class II Ab were detected. Five of them were directed against the DQ incompatibilities of the donor. For example one case report with the mismatch situation HLA A, B, DR, DQ: 0, 1, 2, 2. The not sensitized patient developed anti donor HLA-DQ Ab on day 8 resulting in vascular rejection. Anti donor class I Ab were consecutively observed on day 15. The graft was ectomized on day 22. The class II Ab was detected clearly by PRA-STATâ at day 8, whereas FC-Xm with spleen cells was only weak positive. CDC-PRA and CDC-Xm became positive only after graft ectomy. This study demonstrates that half of our kidney graft recipients with early complications (vascular rejection and/or graft loss) develop alloAb against HLA class II antigens. The data underscore the importance of the HLA class II locus in kidney transplantation.