Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation.
BACKGROUND
Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx).


METHODS
The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx.


RESULTS
Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p < 0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p < 0.001) were associated with lower hazard of BOS.


CONCLUSIONS
Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.
Departments of (a)Pediatrics; Internal Medicine; Surgery; Section of Pulmonary Medicine. Electronic address: hayes.705@osu.edu.
Don
D
Hayes
Surgery.
Sylvester M
SM
Black
Anesthesiology, The Ohio State University College of Medicine, Columbus, Ohio; Department of Anesthesiology and Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Joseph D
JD
Tobias
Departments of (a)Pediatrics; Section of Pulmonary Medicine.
Benjamin T
BT
Kopp
Departments of (a)Pediatrics; Internal Medicine; Section of Pulmonary Medicine.
Stephen E
SE
Kirkby
Skaggs Pharmaceutical Sciences Center, University of Arizona-Tucson College of Pharmacy, Tucson, Arizona.
Heidi M
HM
Mansour
Surgery.
Bryan A
BA
Whitson
D000367:Age Factors; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000077552:Basiliximab; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D016016:Proportional Hazards Models; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013577:Syndrome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006680:HLA Antigens; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab
bronchiolitis obliterans syndrome; hazard risk; human leukocyte antigen; induction therapy; lung transplantation; mismatch; obliterative bronchiolitis; survival