The Clinical Significance of HLA Compatibility Scores in Lung Transplantation

Abstract

Lung transplantation is a life-saving therapeutic option for many chronic end-stage pulmonary diseases, but long-term survival may be limited by rejection of the transplanted organ. Since HLA disparity between donor and recipient plays a major role in rejection, we performed a single center, retrospective observational cohort analysis in our lung transplant cohort (n = 128) in which we calculated HLA compatibility scores for B-cell epitopes (HLAMatchmaker, HLA-EMMA), T-cell epitopes (PIRCHE-II) and missing self-induced NK cell activation (KIR Ligand Calculator). Adjusted Cox proportional hazards model was used to investigate the association between mismatched scores and time to development of donor-specific antibodies (DSA) post-transplant, time to first biopsy-proven acute rejection episode, freedom from CLAD, graft survival and overall survival. For time to first DSA, HLA-EMMA DQB1 scores and PIRCHE-II DQB1 scores were significantly associated with more rapidly developing anti-HLA-DQ antibodies. HLA-EMMA DQB1 score was significantly associated with worse survival. KIR ligand Host-versus-Graft (HvG) mismatches was significantly associated with worse graft survival (CLAD or death) and shorter time to first biopsy-proven rejection when 2 mismatches were present. We demonstrated that HLA-DQB1 compatibility scores and KIR ligand HvG 2 mismatches may allow for identification of recipients at risk of poor long-term outcomes after lung transplantation.