INCREASED RISK OF ACUTE AND CHRONIC REJECTION IN SENSITIZED KIDNEY RECIPIENTS WITH HLA CLASS II-DIRECTED DONOR ANTIGEN-SPECIFIC ANTIBODIES.

Abstract

684 Kidney recipients with preformed anti-HLA antibodies (Abs) have more acute rejection episodes (AR), a higher incidence of chronic rejection (CR), and a lower graft survival rate than unsensitized recipients, even with negative pretransplant crossmatch with donor cells. Recent reports indicate that acute rejection and graft loss correlate more closely with the presence of antibodies detected pretransplant by the ELISA technique than by cytotxicity techniques. However, until recently, the independent detection of HLA class I- vs. class II-directed antibodies was not possible. We utilized a highly sensitive ELISA technique with purified class I or class II antigens allowing for the independent identification of class I- vs. class II-directed Abs (One Lambda, Canoga Park, CA) to determine whether the presence of class II-directed antibodies in addition to class-I-directed antibodies correlated with an increased incidence of AR or CR. We tested sera from 40 kidney recipients who had class I panel reactive Ab > 10% (determined by antiglobulin cytotoxicity technique) at the time of transplant. We determined the frequency of recipients who also had class II-directed antibodies and the incidence of AR and CR. Of these 40 recipients, 25 (63%) also had class II-directed Abs. We observed that 52% (13/25) of recipients with and 53% (8/15) of recipients without class II-directed antibodies experienced AR; thus, the mere presence of class II-directed Abs did not correlate with a higher AR rate. However, this ELISA technique identified 7 recipients with donor class II antigen-specific antibodies; only 1 recipient had a positive B cell cytotoxic crossmatch at the time of transplant. All 7 of these recipients experienced at least 1 AR episode and, to date, 3 have developed CR. Two recipients were shown to have donor class I antigen-specific antibodies detected by ELISA but not by cytotoxic techniques. One had AR, the other did not. None of the recipients with class I only directed antibodies has developed CR. These results suggest that this ELISA technique identifies recipients with class I-directed antibodies who also have class II donor antigen-specific antibodies and are at the highest risk for AR and CR. The availability of this information pretransplant may allow for individualization and optimization of immunosuppression.