Pre-Transplant Panel Reactive Antibody in Lung Transplant Recipients is Associated with Significantly Worse Post-Transplant Survival in a Multicenter Study

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Background

The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction.

Methods

A retrospective study of all first lung transplant recipients from the University of Toronto (November 1983–July 2001, n = 380) and Duke University (April 1992–June 2000, n = 276) was performed. Demographic data, survival information, and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA level was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the Kaplan-Meier method, and groups were compared with the Wilcoxon rank sum test.

Results

Of 656 lung transplant recipients, 101 (15.4%) had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70% vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006, Wilcoxon’s rank sum test) test).

Conclusion

Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments such as plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated.

Section snippets

Methods

A retrospective study was performed at the University of Toronto and at Duke University Medical Center. Patients receiving a second lung transplant were excluded because of the confounding effect related to the increased likelihood of an elevated PRA and worse outcomes compared with first transplants.

There were 380 first lung transplants performed at the University of Toronto between November 1983 and July 2001. All patients received post-operative immunosuppression with cyclosporine A,

Results

During the study period, 656 first lung transplants were performed at the 2 institutions. Of these 656, 101 patients (15.4%) had a PRA greater than zero before transplant, 37 patients (5.6%) had a PRA greater than 10%, and 20 patients (3.0%) had a PRA greater than 25%, which was chosen as the cutoff for a positive result in this study. Their characteristics can be seen in Table 1. The mean PRA of patients with values higher than 25% was 49.5% ± 14.9%. The median value for these patients was

Discussion

Elevated PRA levels, as measured by the CDC-AHG method, are not very common in lung transplant recipients. In renal transplantation, 25% to 50% of patients on the waiting list have a PRA level higher than 20%,30 while 5.5% of heart transplant recipients had high PRA levels before transplant.17 Gender was not predictive of a higher PRA level; however, the relatively small number of patients might have decreased the ability of this study to detect any gender effects on elevated PRA. CDC-AHG is

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