Antigenic responses are hallmarks of fibrotic interstitial lung diseases independent of underlying etiologies.
Yoon, Y. m.; Velez, T. E.; Upadhyay, V.; Vazquez, S. E.; Lee, C. T.; Selvan, K. C.; Law, C. S.; Blaine, K. M.; Hollinger, M. K.; Decker, D. C.; Clark, M. R.; Strek, M. E.; Guzy, R. D.; Adegunsoye, A.; Noth, I.; Wolters, P. J.; Anderson, M. S.; DeRisi, J. L.; Shum, A. K.; Sperling, A. I.
Show abstract
Interstitial lung diseases (ILD) are heterogeneous conditions that may lead to progressive fibrosis and death of affected individuals. Despite diversity in clinical manifestations, enlargement of lung-associated lymph nodes (LLN) in fibrotic ILD patients predicts worse survival. Herein, we revealed a common adaptive immune landscape in LLNs of all ILD patients, characterized by highly activated germinal centers and antigen-activated T cells including regulatory T cells (Tregs). In support of these findings, we identified serum reactivity to 17 candidate auto-antigens in ILD patients through a proteome-wide screening using phage immunoprecipitation sequencing. Autoantibody responses to actin binding LIM protein 1 (ABLIM1), a protein highly expressed in aberrant basaloid cells of fibrotic lungs, were correlated with LLN frequencies of T follicular helper cells and Tregs in ILD patients. Together, we demonstrate that end-stage ILD patients have converging immune mechanisms, in part driven by antigen-specific immune responses, which may contribute to disease progression.
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