HLA-DR incompatibility predicts heart transplant rejection independent of immunosuppressive prophylaxis

To determine whether immunosuppressive prophylaxis reduces the effect of HLA-DR incompatibility on rejection, we compared clinical and immunologic variables of patients given horse antithymocyte globulin, OKT3, or no immunosuppressive prophylaxis. Median follow-up was 27 months. Groups were similar in race; preoperative HLA reactivity; ABO matching; number of HLA-A, -B, -C, and -DR mismatches; and rejection severity. Patients given immunosuppressive prophylaxis were younger (p = 0.04), had a greater frequency of preoperative ischemic disease (p = 0.03), and had a higher 6-month rejection rate (p = 0.02). A highly significant association was found between the number of mismatches at the HLA-DR locus and rejection severity (p = 0.005). Within the OKT3-based immunosuppressive prophylaxis group and the no immunosuppressive prophylaxis group a significant association was found between the number of HLA-DR mismatches and rejection severity (p = 0.01 and p = 0.009, respectively). A similar trend was identified in the group given horse antithymocyte globulin-based immunosuppressive prophylaxis. Logistic regression, used to identify independent predictors of rejection, showed that the number of HLA-DR mismatches and not the use or type of immunosuppressive prophylaxis is significantly associated with rejection (p = 0.0009). One-year patient survival was 83% in the group with two HLA-DR mismatches and 85% in the group with one or no HLA-DR mismatch. Thus the lower rejection rates in patients with one or no HLA-DR mismatch were not associated with a 1-year survival, which was better than that of patients with two HLA-DR mismatches. The potential benefit of HLA-DR matching on rejection and patient survival must be confirmed by larger prospective studies.