Author:
Yoon Young me,Velez Tania E.,Upadhyay Vaibhav,Vazquez Sara E.,Lee Cathryn T.,Selvan Kavitha C.,Law Christopher S.,Blaine Kelly M.,Hollinger Maile K.,Decker Donna C.,Clark Marcus R.,Strek Mary E.,Guzy Robert D.,Adegunsoye Ayodeji,Noth Imre,Wolters Paul J.,Anderson Mark,DeRisi Joseph L.,Shum Anthony K.,Sperling Anne I.
Abstract
SummaryInterstitial 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.
Publisher
Cold Spring Harbor Laboratory