Pre-existing self-reactive IgA antibodies associated with primary graft dysfunction after lung transplantation

Background: Primary graft Dysfunction (PGD) results in significant mortality and morbidity after lung transplantation (LT). The objective of this study was to evaluate if pre-existing antibodies to self-antigens in sera of LT recipients are associated with PGD. Methods: The serum profiles of IgG and IgA autoantibodies were analyzed using a customized proteomic microarray bearing 124 autoantigens. Autoantibodies were analyzed using Mann-Whitney U test or Fisher exact test. The association of the autoantibodies with clinical phenotypes and survival was analyzed by Kaplan-Meier Survival Analysis. Receiver operating curve characteristics (ROC) were calculated to evaluate the predictive value of the autoantibodies for PGD. Results: 51 patients were included in this study. Autoantigen microarray analysis on the pre-transplantation samples identified 17 IgA and 3 IgG autoantibodies which were significantly higher in recipients who developed PGD compared to those who did not (adjusted p <.05 and fold change>1.5). 6 IgA Abs were significantly associated with survival. Taken as a panel, an elevation of 6 IgA Abs had significant predictive value for PGD. Area under the curve value for the panel was 0.9413 for PGD with ROC analysis. Notably, 6 of the 17 IgA autoantigen targets are belong to proteoglycan family of extracellular matrix proteins. Conclusion: Pre-existing IgG and IgA autoantibodies in LT patients correlate with PGD and with survival in a single center, small cohort of lung transplant recipients. Further validation is needed to confirm the findings in the study.