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Previously, we reported that the combination of plasmapheresis (PP) and intravenous immunoglobulin (IVIg) allow sensitized patients to undergo orthotopic heart transplantation (OHT), even across a positive crossmatch. In the current study, the effect of that combination, PP+IVIg, on survival of a larger group of such recipients is investigated. The latter group (I) consisted of 35 sensitized patients who received PP+IVIG together with standard immunosuppressive drugs. Rejection was seen in 11 patients, findings strongly suggestive of a vascular (humoral) being identified in five of those cases. Four deaths occurred, two of them in the immediate post-operative period, one after almost six months, and one after almost two yr post-OHT. Follow-up range 4.5 months to 7.8 yr post-OHT (average=1.1 yr). Patient survival was analyzed after generation of a Kaplan-Meier plot. Comparison with a control OHT group (II) given standard immunosuppressive drugs only (N=276) showed enhanced survival of group I (p=0.0414 by log-rank test). We conclude that the combination of PP and IVIG (i) is associated with declines in T- and B-percent-reactive antibody and in crossmatch positivity, and (ii) is very useful in the management of the sensitized cardiac patient undergoing OHT, often allowing a successful outcome to transplantation in the face of a positive crossmatch.

These data show that aPA are an important risk factor for early renal allograft failure. Furthermore, aPA-positive patients who have no history of hemodialysis are at the greatest risk. Pretransplantation aPA screening of renal transplant candidates forewarns of early graft failure and indicates which patients may benefit from anticoagulant therapy.

An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The method of antibody testing did not have a marked influence on the frequency of antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30% of heart patients, and 31% of liver patients. Among 948 kidney patients who had HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death occurred in 1.4% of total kidney patients and did not correlate to the presence of antibodies. We conclude that patients with posttransplant HLA antibodies indeed have a higher rate of chronic graft failure and that posttransplant antibodies are predictive of chronic rejection.

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Renal allograft thrombosis can cause transplant failure. Because antiphospholipid antibodies (aPA) are associated with thrombosis, we investigated pretransplant sera from patients with early renal allograft failure to determine if aPA were present. Fifty-six final crossmatch (FxM) sera from patients whose transplant failed within 16 days were compared to FxM sera from the next sequential transplant patients. The sera were tested for IgG, IgM, and IgA antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine. aPA were identified in 57 YO of FxM sera from patients with early non-function versus 35 % of FxM sera from patients with functioning grafts (P = 0.02). Historical sera from 11 aPA-positive patients contained aPA up to 18 months prior to transplantation. Since aPA were present in historical sera, testing for aPA can identify certain patients at risk for early allograft failure. The involvement of aPA in early allograft loss is supported by studies demonstrating aPA recovery from an explanted failed transplant.

Data collected prospectively on 3811 renal transplantations performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of donor-recipient HLA-A and HLA-B matching on patient and graft outcome. Well-matched recipients were more likely to have received kidneys from outside their own centers, were more highly presensitized, included fewer blacks, and were more likely to have lost an earlier graft. Multivariate Cox regression analysis that included these and six other potential confounding variables revealed a significant association (P less than 0.001) between good HLA-A and B matching and increased graft survival. The difference in mean (+/- S.E.) actuarial graft survival between recipients worst matched and best matched for HLA-A and B antigens increased with time: 55 +/- 2 per cent as compared with 64 +/- 4 per cent at six months and 18 +/- 4 per cent as compared with 44 +/- 7 per cent at four years. Poor HLA matching of donor with recipient provided the greatest relative risk (2.16) of irreversible graft rejection of all the variables examined. Among patients with functioning grafts, well-matched recipients had lower serum creatinine levels and received significantly smaller amounts of glucocorticoids. Our findings indicate that good HLA-A and B matching is highly dependent on a system for sharing organs among institutions, and results in decreased graft rejection, better long-term graft function, and less need for post-transplantation immunosuppression.