Use of hearts transplanted from donors with atraumatic intracranial bleeds.
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Biomedical subjects
Publications and source records attributed to D Gjertson.
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BACKGROUND: Allocation of cadaver kidneys by graded human leukocyte antigen (HLA) compatibility scoring arguably has had little effect on overall survival while prejudicing the transplant candidacy of African-American and other hard to match populations. Consequently, matching has been proposed of deduced amino acid residues of the individual HLA molecules shared by cross-reactive antigen groups (CREGs). We have examined the circumstances under which compatibility with either method impacted graft survival. METHODS: Using Cox proportional hazards regression modeling, we studied the relationship between levels of conventional HLA mismatch and other donor and recipient factors on primary cadaver kidney survival between 1981 and 1995 at the University of Pittsburgh (n=1,780) and in the United Network for Organ Sharing (UNOS) Scientific Registry during 1991-1995 (n=31,291). The results were compared with those obtained by the matching of amino acid residues that identified CREG-compatible cases with as many as four (but not five and six) HLA mismatches. RESULTS: With more than one HLA mismatch (> 85% of patients in both series), most of the survival advantage of a zero mismatch was lost. None of the HLA loci were "weak." In the UNOS (but not Pittsburgh) category of one-HLA mismatch (n=1334), a subgroup of CREG-matched recipients (35.3%) had better graft survival than the remaining 64.7%, who were CREG-mismatched. There was no advantage of a CREG match in the two- to four-HLA incompatibility tiers. Better graft survival with tacrolimus was observed in both the Pittsburgh and UNOS series. CONCLUSIONS: Obligatory national sharing of cadaver kidneys is justifiable only for zero-HLA-mismatched kidneys. The potential value of CREG matching observed in the one-HLA-mismatched recipients of the UNOS (but not the Pittsburgh) experience deserves further study.
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Unrelated donor bone marrow transplants have been associated with relatively high rates of acute graft-vs.-host disease and treatment-related mortality. These complications reflect histo-incompatibility between donor and recipient. Molecular technology has recently been applied to HLA typing to identify alleles not distinguishable with serologic typing techniques. We report results in 92 unrelated marrow transplant recipients who were HLA seroidentical with donor HLA-A, -B, and -DR antigens and assess the effect of DR beta 1 and DQ beta compatibility using sequence specific oligonucleotide primers. Forty-eight patients received T-cell depleted marrow grafts, and 44 received unmodified grafts. Among recipients of unmodified marrow grafts, matching for both DR beta 1 and DQ beta reduced the rate of grade 3-4 acute graft-vs.-host disease to 38 +/- 20% vs. 73 +/- 20% among recipients mismatched for either allele (p = 0.02). This difference was not observed in recipients of T-cell depleted marrow grafts. Multivariate analysis confirmed matching for both DR beta 1 and DQ beta loci (p = 0.015), and receiving a T-cell depleted graft (p = 0.008) independently predicted for reduced risk of grade 3-4 acute graft-vs.-host disease. In conclusion, both DR beta 1 and DQ beta appear biologically important for development of acute graft-vs.-host disease in patients receiving unmanipulated marrow grafts for unrelated donor transplant.
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The difficulty in achieving long-term survival is demonstrated by the fact that an improvement of 30 percentage points in 1-year cadaver donor survival resulted in only a 10-percentage point improvement over 20 years. In early transplants from 1965 to 1974, the 20-year survival rate of HLA identical siblings was 46%, of parental donors 27%, and of cadaver donors 12%. More recent grafts, performed since 1987, had a projected survival of 57% for identical donors, 30% for parental donors, and 18% for cadaver donors. With respect to HLA matching for cadaver donor kidney transplants, a 0 AB-antigen mismatch produced higher graft survival than did mismatched transplants during the 20-year period from 1965 to 1984. After the introduction of HLA Class II typing in 1980 and general improvements in typing for transplants performed after 1987, the 0 ABDR-mismatched grafts have a projected 20-year survival of 40%. The projected survival rates for transplants with one or more mismatches fall progressively to 13% for transplants that have 6 ABDR mismatches. Thus, the success due to HLA matching has improved ever since the introduction of cyclosporine because of the concurrent improvements in tissue typing for Class I and Class II specificities.
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The subjects of this study were transplant recipients entered in the UCLA Registry file since 1984 and in the UNOS Registry since 1987. [table: see text] 5. Based on the data above, we conclude that the near 20% loss rate in the first year can be roughly allocated as follows: death 3%, technical 3%, agonal kidney damage 6%, and histocompatibility differences 7%. 6. The quality of HLA typing was assessed by examining the frequencies of the various specificities reported for cadaver donors in 8 yearly periods from 1984 to 1991. The A and B loci specificities were remarkably constant. The DR specificities were still undergoing stabilization. 7. No urine output on the first day, which occurred in approximately 10% of the first cadaver-donor transplants, resulted in about a 20 percentage point lower graft survival rate at 1 year. 8. Anuria on the first day increased with cold ischemia time, donor age, cerebral vascular accident donors, and retransplant recipients. 9. Graft survival with anuria on the first day and: [table: see text] 10. When dialysis was required during the first week, there was an approximate 15 percentage point decrease in 1-year graft survival in 25% of the patients. 11. One rejection in the first hospitalization period resulted in 67% 1-year graft survival. More than 1 rejection led to 57% 1-year graft survival. 12. Serum creatinine at discharge was an accurate indicator of subsequent graft survival. Approximately a 7 percentage point drop in 1-year graft survival was noted with each unit of serum creatinine above 2.0 mg/dl.
From studies of 16,993 reactions in the microlymphocyte cytotoxicity test, we concluded that automatic fluorescent readings are comparable to those produced by visual readings with eosin dye exclusion. The r values (counting only strong reactions as positive) were as follows: 0.94 fluorescence machine versus visual fluorescence reading; 0.96 eosin visual reading, reader 1 versus reader 1; 0.97 eosin visual reading, reader 2 versus reader 2; 0.91 eosin visual reading, reader 1 versus reader 2; 0.98 fluorescence machine 1 versus machine 1; 0.98 fluorescence machine 2 versus machine 2; 0.96 fluorescence machine 1 versus machine 2; 0.92 fluorescence machine versus eosin visual reading; It was further shown that there was 93% concordance in assignment of HLA specificities between machine-assigned specificities and assigned by an experienced technologist. Most of the extra reactions obtained by fluorescence were in the crossreactive groups. Thus, the extra positive reactions obtained by the machine were likely to be the result of greater sensitivity than detection of random extraneous reactions.
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Five subtypic specificities of Bw22 were defined using 38 informative local and Seventh Histocompatibility Workshop sera: Bw54, 22.2, J2, Bw42, and a new Bw22 associated antigen Te90. The previously defined specificity, 22.1, associated with Cw3, could not be distinguished from Bw54 in this study. Marked restriction in the distribution of four Bw22 specificities (Bw54 excepted) in white, Mexican, black, and Oriental populations was described and provided supporting evidence for the identification of these antigens.
Using HLA tissue typing as the basic genetic test along with ABO and haptoglobin typing, it is generally possible either to exclude a putative father conclusively or, in nonexclusion cases, to assign a greater than 95% probability of paternity. In 22 of 53 nonexclusion cases, the putative father had a probability of paternity above 99% based on these genetic tests.
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