HLA-DR3 associated with improved kidney transplant survival

Using the National Kidney Recipient Pool and selecting all patients who were HLA-DR typed, immunized by either transfusion or kidney allograft, and had recorded cytotoxic antibody against a panel of lymphocytes, we found significantly lower levels of cytotoxic antibody in patients with HLA-DR3 (p < 0.05). Moreover, when we examined patients with only HLA-DR3 (presumed homozygous) we found that the low response effect was even stronger and was significant at 30%, 67%, or 90% cytotoxic antibody cutoffs. One of the immediate predictions of postulating that homozygous HLA-DR3 patients are low responders is that these patients should have better kidney transplant survival. Indeed, when we examined transplant survival in HLA-DR3 homozygous transplant patients and non-HLA-DR3 patients, the 1-year survival was 74% ± 9% vs. 49 ± 4%, respectively. When one stratifies the data for transfusion effect, the 0-4 transfusion category shows 43% ± 5% survival for non-HLA-DR3 recipients vs. 79% ± 10% for HLA-DR3 only recipients. These data strongly suggest HLA-DR3 individuals have a low responsiveness to histocompatibility antigens.