Skip to main content

Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

American journal of respiratory and critical care medicine

Authors: Nina Wyss, Fiamma Berner, Vincent Walter, Ann-Kristin Jochum, Mette T Purde, Marie-Therese Abdou, Tobias Sinnberg, Kathrin Hofmeister, Oltin T Pop, Omar Hasan Ali, Jens Bauer, Hung-Wei Cheng, Mechthild Lütge, Niklas Klümper, Stefan Diem, Zeynep Kosaloglu-Yalcin, Yizheng Zhang, Laura Sellmer, Boris Macek, Julia Karbach, David König, Heinz Läubli, Lars Zender, Britta S Meyer, Christoph Driessen, Christian M Schürch, Wolfram Jochum, Teresa Amaral, Lucie Heinzerling, Antonio Cozzio, Ahmed N Hegazy, Tino Schneider, Martin H Brutsche, Alessandro Sette, Tobias L Lenz, Juliane Walz, Hans-Georg Rammensee, Martin Früh, Elke Jäger, Burkhard Becher, Amanda Tufman, Nicolas Nuñez, Markus Joerger, Lukas Flatz

RATIONALE: Immune checkpoint inhibitor-related pneumonitis is a serious autoimmune event affecting up to 20% of patients with non-small cell lung cancer, yet the factors underpinning its development in some patients and not others are poorly understood.

OBJECTIVES: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis.

METHODS: The study cohort consisted of non-small cell lung cancer patients who gave blood samples before and during immune checkpoint inhibitor treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with non-small cell lung cancer and patients with melanoma.

MEASUREMENTS AND MAIN RESULTS: Across both cohorts, patients who developed pneumonitis had higher pre-treatment levels of immunoglobulin G autoantibodies targeting surfactant protein-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4 interferon-gamma-positive surfactant protein B-specific T cells, and expanding T cell clonotypes recognizing this protein, accompanied by a pro-inflammatory serum proteomic profile.

CONCLUSIONS: Our data suggest that the co-occurrence of surfactant protein-B-specific immunoglobulin G autoantibodies and CD4 T cells is associated with the development of pneumonitis during ICI therapy. Pre-treatment levels of these antibodies may represent a potential biomarker for elevated risk of developing pneumonitis and on-treatment levels may provide a diagnostic aid.

PMID: 38626354

Participating cluster members