POST-TRANSPLANT ANTI-MHC CLASS II ANTIBODIES ADVERSELY AFFECT KIDNEY AND KIDNEY/PANCREAS OUTCOMES.
RP Pelletier, PW Adams, PK Hennessy, K Orosz, J Martin, CG Orosz The Ohio State University Medical Center Clinical Histocompatibility Laboratory

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We have evaluated the clinical impact of alloantibodies directed at MHC Class I vs Class II molecules that develop in patients during the post-transplant period. This study involved 247 primary kidney and simultaneous kidney-pancreas recipients transplanted between 8/83 and 12/99 whose sera were analyzed from 1 to 192 months post transplant (mean=2.6 years +/- 2.4 years). Alloantibodies were detected using One Lambda FlowPRA beads and alloantibody production was defined as a flow reactivity >6%. All patients with detectable alloantibodies prior to transplantation were excluded from this study. The incidence of alloantibody production post-transplant for MHC Class I-reactive alloantibodies was 6.5% (16/247) and 18% (45/247) for MHC Class II-reactive alloantibodies. We observed that 32% (23/73) of the patients who developed acute rejection either developed MHC I-reactive or MHC II-reactive alloantobodies, while only 16% (27/174) of the patients without acute rejection had detectable post-transplant alloantibodies (p=0.004). Univariate analysis demonstrated a significant correlation between the presence of MHC Class II-reactive antibodies and acute rejection (p=0.005). A significant correlation was also observed for MHC Class I-reactive antibodies and acute rejection (p=0.02). This univariate analysis is confounded by the fact that 11 of 16 of the patients who developed MHC Class I-reactive antibodies concomitantly produced MHC Class II-reactive antibodies. Evaluation of anti-MHC Class I and Class II antibodies as independent predictors of acute rejection using multivariate analysis revealed that anti-MHC Class II (p=0.006), but not anti-MHC Class I (p=ns) is a significant predictor of acute rejection. Univariate analysis also showed a significant correlation between the post-transplant production of MHC Class II-reactive antibodies and chronic rejection (p=0.001). In contrast, the presence of MHC Class I-reactive antibodies showed no correlation with the development of chronic rejection(p=0.192). In this small series, univariate analysis failed to demonstrate a significant correlation between the degree of HLA mismatch and the production of de novo post transplant alloantibody . We conclude that the development of MHC Class II-reactive antibodies, but not MHC Class I-reactive antibodies, correlates with post-transplant acute rejection and chronic rejection.