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Kidney graft failure and presensitization against HLA Class I and Class II antigens1

Background. It is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have an increased graft rejection rate. However, the individual contribution of anti-HLA class I and class II antibodies to this phenomenon is poorly understood. We investigated the clinical relevance of preformed anti-HLA class I and class II antibodies on graft outcome in more than 4000 kidney recipients. Methods. Pretransplant sera of 4136 cadaver kidney recipients from 28 transplant centers were tested in ELISA for IgG-anti-HLA class I and IgG-anti-HLA class II antibodies. The influence of antibody reactivity on graft survival was analyzed. Results. Four hundred eighty of the anti-HLA class I antibody-positive recipients had a graft survival rate at 2 years of 77±2%, compared with an 84±1% rate in 3656 anti-HLA class I antibody-negative recipients (P <0.0001), and 770 anti-HLA class II-positive recipients had a graft survival rate of 79±2%, compared with an 84±1% rate in 3366 anti-HLA class II-negative patients (P <0.0001). Importantly, good 2-year graft survival rates of 85±3% and 84±2%, respectively, were observed in 206 anti-HLA class I-positive/class II-negative and 496 anti-HLA, class I-negative/class II-positive recipients. In contrast, the 274 recipients positive for both types of antibodies showed a poor graft survival rate of 71±3% (P <0.0001). Among 853 patients who received a well-matched kidney (0 or 1 HLA-A+B+DR mismatch), sensitization against either class I or class II, or both, had no deleterious effect. However, in 113 class I and class II antibody-positive patients who received a kidney with ≥3 HLA-A+B+DR mismatches, the 2-year graft survival rate was only 60±5%. Conclusion. Presensitization of first kidney transplant recipients against either HLA class I or class II is of no clinical consequence, whereas sensitization against both HLA class I and class II results in increased rejection of HLA mismatched grafts.