Self-reactive antibodies associated with bronchiolitis obliterans syndrome subtype of chronic lung allograft dysfunction

Background: Chronic Lung Allograft Dysfunction (CLAD) remains the major limitation in long term survival after lung transplantation. Our objective is to evaluate for the presence of autoantibodies to selfantigens, which is a pathway along with complex interplay with immune as well as non-immune mechanisms that leads to a fibroproliferative process resulting in CLAD. Methods: Serum profiles of IgG autoantibodies were evaluated using customized proteomic microarray with 124 antigens. Output from microarray analyzed as antibody scores is correlated with bronchiolitis obliterans (BOS) subtype of CLAD using Mann-Whitney U test or Fisher exact test. Autoantibodies were evaluated for their predictive value for progressive BOS using a Cox proportional hazard model. BOS free survival and overall survival was analyzed using Kaplan-Meier survival analysis. Results: Fortytwo patients included in the study are grouped into stable BOS and progressive BOS for comparisons. Pulmonary fibrosis is the major indication for lung transplantation in our cohort. Progressive BOS group had significantly worse survival (p < 0.005). Sixteen IgG autoantibodies are significantly elevated at baseline in progressive BOS group. Six among them correlated with worse BOS free survival (p < 0.05). In addition, these six IgG autoantibodies remain elevated at three months and one year after lung transplantation. Conclusion: Pre-existing IgG autoantibodies correlate with progressive BOS and survival in a single center, small cohort of lung transplant recipients. Further validation with larger sample size, external cohort and confirmation with additional tissue, bronchoalveolar lavage samples are necessary to confirm the preliminary findings in our study. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.

Automated summary

This study found that pre-existing elevated IgG autoantibodies are significantly correlated with progressive BOS and worse survival in lung transplant recipients. The findings suggest important implications for predicting long term survival after lung transplantation.