Human immunology
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The predictive power of a positive B-cell crossmatch remains controversial due to the presence of cofactors, such as sensitization and human leukocyte antigen (HLA) mismatch levels. UNOS OPTN/Scientific Registry data were analyzed on 9031 cadaveric kidney graft recipients who were B-cell crossmatched during 1994 and 1995 for graft outcome. This 2-year time period was chosen so that most US transplant recipients in this study would have had a similar regimen of immunosuppression consisting of prednisone, Sandimmune, and azathioprine The two patient groups that were analyzed were B-pos (n = 336) and B-neg (n = 8,695). ⋯ HLA-DR mismatch levels in both patient groups were not different (p = 0.109). There was a 68% increase in the odds of 3-month graft loss in B-pos versus B-neg recipients (multivariate logistic regression analysis p = 0.054, 95% confidence interval 0.99-2.85). In conclusion, a B-pos crossmatch in primary and regraft recipients, including a sensitized subset, is predictive of inferior kidney graft outcome.
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We studied late graft rejection in a patient who had received a kidney transplant 9-10 years earlier from his mother and who had been off all immunosuppressive drugs for 7 years at the time of graft rejection onset. The mother differed for one HLA-A (A3) and one HLA-B (B62) antigen but had only a subtype mismatch at the HLA-DR beta 1 locus (donor: DR beta 1*1104; recipient: DR beta 1*1102). A gradual rise in serum creatinine from 1.8 to 2.0 mg/dl at year 9 prompted a biopsy, which was negative for rejection (focal infiltrates but no tubulitis). ⋯ Similarly, we found an anti-HLA class II donor-specific antibody in serum that appeared to be crossreactive with DR beta 1*1104 and DR beta 1*1101 but not with the recipient DR beta 1*1102 antigen. The data support the idea of a profound unresponsive state at both the cellular (DTH) and humoral level toward maternal HLA class I antigens that was not reversed even during late cellular rejection, despite the release of high levels of soluble HLA class I. Furthermore, the data suggest that DTH recovery was a close correlate of the onset of rejection and this "indirect" alloresponse, like the anti-donor alloantibody response that followed, was directed not to noninherited maternal HLA-A,B antigens but to the maternal HLA DR beta 1*1104 subtype.
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The impact of donor-recipient DPA1 and DPB1 matching was examined in 122 unrelated bone marrow transplant pairs. All pairs were serologically matched at the time of transplantation for HLA class I and II and a majority also DRB1 allele matched. Retrospective A, B, C, DRB1, DQA1, DQB1 in addition to DPA1 and DPB1 allele matching was performed by molecular techniques. ⋯ This beneficial effect remained when allele mismatches at HLA-A, B, C, DRB1, DQA1, DQB1 were excluded (p = 0.05, p = 0.03, respectively). There was a significant association of increased frequency of severe GVHD (grades III-IV) compared to mild GVHD (grades I-II) with DPB1 mismatched transplants compared to DPB1 matched transplants (p = 0.04). In DPB1 mismatched transplants an association between patient survival and matching for individual DPB1 polymorphic regions was not observed; however in the HLA-A, B, DRB1, DQA1, DQB1 allele matched transplants a non significant increase in the frequency of Grade IV GVHD was observed in recipients who were negative compared to those who were positive for DPB1 alleles coding for glutamic acid at position 69.