Antigenic responses are hallmarks of fibrotic interstitial lung diseases independent of underlying etiologies.

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.

Déclaration de conflit d'intérêts

Conflicts of Interest M.E. Strek received grants from editorial assistance from Boehringer Ingelheim and personal fees from Fibrogen. A. Adegunsoye received grants and personal fees from Boehringer Ingelheim, Roche, Inogen, and Medscape. P. J. Wolters received grants from Roche, Sanofi, Pliant, Boehringer Ingelheim, and personal fees from Sanofi, Boehringer Ingelheim, and Blade Therapeutics. M. Anderson owns stock in Medtronic and Merck and has consulted for Sana and Imcyse. J.L. Derisi is a paid scientific consultant for The Public Health Company, Inc., Allen & Co., and Delve Bio. There is no direct overlap between the current study and these consulting duties. These authors have no additional financial interests. The other authors have no conflicting financial interests.