Clinical histocompatibility testing--1979. Proceedings of the fifth annual meeting of the American Association for Clinical Histocompatibility Testing.
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The disparity index is an expression of histocompatibility difference between two siblings with identical human leukocyte antigen (HL-A) type who are nonreactive in mixed leukocyte culture (MLC) test. This index is derived from a third-party MLC test. The disparity index was found to be correlated with the severity of graft-versus-host reaction in bone marrow transplantation between HL-A-identical siblings. The disparity index may prove to be a useful means of predicting the severity of graft-versus-host reaction and the outcome of bone marrow graft when HL-A- and MLC-matched sibling donors are studied. The third-party MLC test is offered as a new method of histocompatibility testing. It may provide a useful model for the study of immunogenetics relative to so-called weaker histocompatibility determinants in man and experimental animals.
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UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.
Histocompatibility testing has been performed in the families of 20 patients with aplastic anemia or acute leukemia, in order to identify a compatible donor for marrow transplantation. In several cases, the interpretation of the tests has been difficult because of abnormalities in the immune reactivity of patients' lymphocytes. Humoral or cellular immunization against donor incompatible antigens seems to prevent a "take" of the graft or a subsequent hematological remission.
Histocompatibility testing prior to kidney transplantation is an established necessity. Recipient sensitization to HLA specificities affects the efficacy of the lymphocytotoxic cross-match and influences the achievable HLA mismatch. Within Europe most cadaver donor kidneys are allocated on the basis of minimum histocompatibility mismatch contrasting with the North American system which allows for exchange of kidneys only where there is no detectable donor/recipient mismatch. There is also a contrast between the immunosuppression protocols used in these continents with, in general, more aggressive regimens used in North America. In the 1990s there has been considerable refinement in the techniques available to histocompatibility laboratories for definition of HLA phenotypes and genotypes and some obstacles to successful transplantation have been overcome. We review some of these changes with particular reference to our own experience.
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The World Marrow Donor Association has formulated guidelines for establishing the extent and quality of histocompatibility testing for unrelated donor registries, umbilical cord blood banks, and transplant centers involved in international exchange of hematopoietic stem cells for allogeneic transplantation. The ability to identify unrelated stem cell donors in one country for patients in another country requires cooperation and standardization in many areas. The adoption of guidelines for histocompatibility testing, such as those summarized in this report, will facilitate these opportunities and rapidly provide accurately typed donors for patients in need.
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Clinical histocompatibility testing has now developed to a stage where it is possible to select related bone marrow donors for some patients, when HLA genotypically identical siblings are not available. The most common type of such donors are the HLA phenotypically or HLA-D phenotypically identical related donors. The HLA-D homozygous recipient offers special options, since these patients can potentially receive bone marrow transplants from any of the parents or from HLA-haploidentical siblings. The studies in SCID have demonstrated that HLA-D compatibility in spite of HLA-A or B incompatibilities can be tolerated and there is now accumulating evidence that even patients with aplastic anemia or acute leukemia can be successfully treated with such bone marrow grafts.
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