Humoral Risk Factors Associated to Allograft Dysfunction after Lung Transplantation: The Alert of Non-HLA Auto Antibody and HLA Donor Specific Antibody (DSA) with Non-DSA HLA Antibody

Purpose Growing evidence has indicated the negative impact of non-HLA auto antibody (NHAuAb) on organ transplantation. Donor specific antibody (DSA) after lung transplantation (LuT) has been observed frequently with de novo Non-DSA (dN-DSA) HLA antibody. This study investigates the deleterious role of post-LuT NHAuAb and dN-DSA synergism to DSA in allograft damage. Methods We retrospectively analyzed NHAuAb and de novo DSA (dDSA)/dN-DSA data collected from recipients who underwent LuT during 2012-2016. NHAuAbs were detected using LABScreen™ Autoantibody (>95% non-sensitized subjects as cut-off). HLA antibody was tested by LABScreen™ SAB (MFI≥ 1000 as cut-off). Clinical Antibody Mediated Rejection (cAMR, with acute graft dysfunction) and Chronic Lung Allograft Dysfunction (CLAD) were assessed for LuT outcomes. Results CXCL9, AURKA, REG3A, IFNγ, FLRT2, GDNF, HNRNPK, CXCL10, PLA2R, and Collagen IV detected from 111 patients’ sera drawn at DSA peak phase showed significant association to total AMR, but only FLRT2 (P Conclusion Distinct clinical phases presented specific NHAuAb profiles. Multiple NHAuAbs, especially LG3, PKC-Z, and PECR, which were preformed and persistent, promoted chronic graft dysfunction. HLA-dDSA augmented by dN-DSA (most likely due to shared targeting epitopes) and NHAuAbs of FLRT2, GDNF, and CXCL10 were related to acute graft injury. These HLA and non-HLA humoral risk factors warrant timely enhanced immune therapy to prevent final allograft failure.