Chest
Volume 144, Issue 1, July 2013, Pages 226-233
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Original Research
Transplantation
Implications for Human Leukocyte Antigen Antibodies After Lung Transplantation: A 10-Year Experience in 441 Patients

https://doi.org/10.1378/chest.12-0587Get rights and content

Background

Long-term survival after lung transplant is limited by the development of chronic and progressive airflow obstruction, a condition known as bronchiolitis obliterans syndrome (BOS). While prior studies strongly implicate cellular rejection as a strong risk factor for BOS, less is known about the clinical significance of human leukocyte antigen (HLA) antibodies and donor HLA-specific antibodies in long-term outcomes.

Methods

A single-center cohort of 441 lung transplant recipients, spanning a 10-year period, was prospectively screened for HLA antibodies after transplant using flow cytometry-based methods. The prevalence of and predictors for HLA antibodies were determined. The impact of HLA antibodies on survival after transplant and the development of BOS were determined using Cox models.

Results

Of the 441 recipients, 139 (32%) had detectable antibodies to HLA. Of these 139, 54 (39%) developed antibodies specific to donor HLA. The detection of posttransplant HLA antibodies was associated with BOS (HR, 1.54; P = .04) and death (HR, 1.53; P = .02) in multivariable models. The detection of donor-specific HLA antibodies was associated with death (HR, 2.42; P < .0001). The detection of posttransplant HLA antibodies was associated with pretransplant HLA-antibody detection, platelet transfusions, and the development of BOS and cytomegalovirus pneumonitis.

Conclusions

Approximately one-third of lung transplant recipients have detectable HLA antibodies, which are associated with a worse prognosis regarding graft function and patient survival.

Section snippets

Study Cohort

Adults (≥18 years old) receiving a first, cadaveric lung transplant at Duke University Medical Center between January 1, 2000, and October 1, 2008, with at least 30-day survival were eligible for this study. Multiorgan, living lobar, and retransplant recipients were excluded. All recipients received standardized immunosuppression, pulmonary function tests, and transbronchial biopsies as described in the supplemental material (e-Appendix 1).17 The study was approved through the Duke University

Study Cohort Demographics and HLA Evaluation

There were 460 lung transplant recipients who met initial inclusion criteria and were eligible for analysis. A total of 5,813 individual serum samples were evaluated for HLA antibodies, including 2,119 pretransplant samples and 3,694 posttransplant samples. Of these 460 recipients, 19 were subsequently excluded from the analysis because they had no posttransplant HLA-antibody tests. Of the remaining 441 subjects, 139 (32%) had detectable HLA antibodies; these composed the positive HLA-antibody

Discussion

In this large cohort of 441 lung transplant recipients, we have found a strong association between posttransplant HLA antibodies and the subsequent development of BOS and worse survival. Furthermore, the detection of DSA, particularly DSA class II, was associated with significantly worse survival than simply the presence of HLA antibodies. Although somewhat surprising, DSA was not associated with BOS. Our results add to the growing interest in the clinical significance of HLA antibodies by

Acknowledgments

Author contributions: Dr Snyder had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Snyder: contributed to study design, data analysis, manuscript preparation, and served as principal author.

Ms Wang: contributed to data collection and analysis and review of the manuscript.

Dr Chen: contributed to manuscript preparation and review.

Dr Reinsmoen: contributed to manuscript preparation and review.

Ms

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Funding/Support: This work was supported by the National Institutes of Health (NIH) [grant KL2RR024127] and the American Society of Transplantation Clinical Faculty Development Award (Dr Snyder), and by the NIH/National Heart Lung and Blood Institute SCCOR [grants 1P50-HL084917-01 and K24-091140-01] (Dr Palmer).

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