Pre- and posttransplantation immunologic monitoring assays for human cardiac transplantation.
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Biomedical subjects
Publications and source records attributed to F Thomas.
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71 recipients of cadaver primary and secondary renal transplants were investigated in a prospective randomised double-blind study. Patients were given one of two rabbit antilymphocyte globulin (A.L.G.) preparations made by similar techniques but differing in potency as measured by skin-graft prolongation in rhesus monkeys. Patient selection and management were otherwise similar. A statistically significant difference (P less than 0-05) in graft survival (78% vs. 42%) developed between the two groups at a mean follow-up of 18-4 months and patient entry into the study was terminated. After a 3-5 year interval from the start of the trial the double-blind code was broken. It was found that the high-potency-A.L.G. group had better graft survival and fewer rejection episodes (P less than 0-05) than the moderate-potency group. The results suggest that preclinical testing of A.L.G. by the primate skin graft test can be a valid indicator of the potential efficacy of an A.L.G. preparation in renal-transplant recipients. It is suggested that quality-control standards may improve the clinical results of A.L.G. therapy.
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In these studies, pretransplant testing of donor-recipient compatibility was performed in 10 related donor and 26 cadaveric renal transplants using a variety of cell-mediated immunity tests. Mixed lymphocyte culture results did not correlate with acute rejection (AR), acute irreversible rejection, or chronic rejection (CR). Lymphocyte-mediated cytolysis also did not correlate with AR, acute irreversible rejection, or CR. Cell-mediated lympholysis correlated with AR but not with acute irreversible rejection or CR. Antibody-dependent cell-mediated cytolysis (ADCMC) was positive pretransplant in 13 (36%) of the recipients. Of the positive patients, 4 had early severe AR and 9 developed typical CR. Of these 13 patients, 9 or 69% lost graft function to rejection whereas only 3 of 20 (15%) of ADCMC-negative patients lost graft function because of rejection (P less than 0.05). In summary, cell-mediated lympholysis testing demonstrated a capability to predict AR episodes. The most useful pretransplant monitoring assay in this patient series was the ADCMC assay. A positive ADCMC against donor cells pretransplant indicates a relatively poor prognosis for long-term graft survival.
In this study a variety of cell-mediated immunity responses were performed in long-term (2 to 12 year) human leukocyte antigen-A (HLA) nonidentical renal transplant patients. All patients showed mixed lymphocyte culture (MLC) stimulation against donor, indicating a lack of tolerance. Of successful long-term transplant patients, 73 percent showed high serum levels of MLC-blocking activity. A consistent association of successful long-term transplantation and a specific defect in recipient ability to generate cytotoxic cells against donor was seen at the 8 to 12 year level. A close association of lymphocyte-dependent activity (LDA) and clinical chronic rejection was found, and LDA could be identified prior to the onset of clinical chronic rejection in most cases. Four patients had a positive LDA assay prior to transplant and all four went on to develop chronic rejection. Recipients taking immunosuppressive drugs within 24 hours of testing had a deficient capability to generate cytotoxic effector cells against indifferent individuals. These findings demonstrate a consistent association of in vitro cell-mediated immunity parameters and in vivo transplant function and may represent a valuable immunological monitoring system for long-term recipient follow-up.
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