(300) The Significant Impact of HLA Homozygosity on Sensitization, Chronic Lung Allograft Dysfunction and Overall Survival

PurposeHLA Sensitization is an important disparity which limits access to lung transplantation (LTx). HLA Mismatching is the foundation of this sensitization, therefore HLA homozygous loci increases the risk of sensitization. We retrospectively analyzed a well characterized lung transplant cohort to determine the association between HLA homozygosity and sensitization, rejection and survival.MethodsA retrospective analysis was performed on 565 LTx recipients (between 2008-2020), comparing HLA typing and clinical outcomes. HLA typing was performed by NGS or Luminex SSO (HLA-A; B; C; DRB1; and DQB1). Pre- and post-transplant calculated panel reactive antibody (cPRA) for HLA antibody specificities (MFI>2000) was derived. Kaplan Meier analysis with log-ranked tests compared homozygosity groups.ResultsPre and post LTx cPRA increased as number of homozygous loci increased. In pre LTx patients with ≥3 HLA homozygous loci there was a 33% increase in the proportion of those with a baseline cPRA >50%, compared to no homozygous loci. HLA homozygosity for HLA-DR was significantly associated with freedom from chronic lung allograft dysfunction (CLAD) (p<0.05) (Fig. 1a) and overall survival (p<0.05) (Fig. 1b). When both HLA-DR and DQ loci were homozygous there was a reduction in freedom from CLAD (Figure 1c) and overall survival (p<0.01) (Figure 1d).ConclusionHLA-DR and DQ homozygosity in patients increases the risk of sensitization pre and post LTx, CLAD and decreases survival. Consideration should therefore be given to donor selection, avoidance of blood products and enhanced post LTx immunologic monitoring for patients with homozygosity of either HLA-DR or DQ loci. HLA Sensitization is an important disparity which limits access to lung transplantation (LTx). HLA Mismatching is the foundation of this sensitization, therefore HLA homozygous loci increases the risk of sensitization. We retrospectively analyzed a well characterized lung transplant cohort to determine the association between HLA homozygosity and sensitization, rejection and survival. A retrospective analysis was performed on 565 LTx recipients (between 2008-2020), comparing HLA typing and clinical outcomes. HLA typing was performed by NGS or Luminex SSO (HLA-A; B; C; DRB1; and DQB1). Pre- and post-transplant calculated panel reactive antibody (cPRA) for HLA antibody specificities (MFI>2000) was derived. Kaplan Meier analysis with log-ranked tests compared homozygosity groups. Pre and post LTx cPRA increased as number of homozygous loci increased. In pre LTx patients with ≥3 HLA homozygous loci there was a 33% increase in the proportion of those with a baseline cPRA >50%, compared to no homozygous loci. HLA homozygosity for HLA-DR was significantly associated with freedom from chronic lung allograft dysfunction (CLAD) (p<0.05) (Fig. 1a) and overall survival (p<0.05) (Fig. 1b). When both HLA-DR and DQ loci were homozygous there was a reduction in freedom from CLAD (Figure 1c) and overall survival (p<0.01) (Figure 1d). HLA-DR and DQ homozygosity in patients increases the risk of sensitization pre and post LTx, CLAD and decreases survival. Consideration should therefore be given to donor selection, avoidance of blood products and enhanced post LTx immunologic monitoring for patients with homozygosity of either HLA-DR or DQ loci.