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Leuschner, G. ; Semenova, A. ; Mayr, C. ; Kapellos, T. ; Ansari, M. ; Seeliger, B.* ; Frankenberger, M. ; Kneidinger, N.* ; Hatz, R.A.* ; Hilgendorff, A. ; Prasse, A.* ; Behr, J.* ; Mann, M.* ; Schiller, H.

Mass spectrometry-based autoimmune profiling reveals predictive autoantigens in idiopathic pulmonary fibrosis.

iScience 26:108345 (2023)

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	Open Access Gold

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Autoimmunity plays a role in certain types of lung fibrosis, notably connective tissue disease-associated interstitial lung disease (CTD-ILD). In idiopathic pulmonary fibrosis (IPF), an incurable and fatal lung disease, diagnosis typically requires clinical exclusion of autoimmunity. However, autoantibodies of unknown significance have been detected in IPF patients. We conducted computational analysis of B cell transcriptomes in published transcriptomics datasets and developed a proteomic Differential Antigen Capture (DAC) assay that captures plasma antibodies followed by affinity purification of lung proteins coupled to mass spectrometry. We analyzed antibody capture in two independent cohorts of IPF and CTL-ILD patients over two disease progression time points. Our findings revealed significant upregulation of specific immunoglobulins with V-segment bias in IPF across multiple cohorts. We identified a predictive autoimmune signature linked to reduced transplant-free survival in IPF, persisting over time. Notably, autoantibodies against thrombospondin-1 were associated with decreased survival, suggesting their potential as predictive biomarkers.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Components Of The Immune System ; Immune System ; Immunological Methods ; Proteomics; Cell Differentiation; B-cells; Lung; Identification; Pirfenidone; Prevalence; Target

ISSN (print) / ISBN 2589-0042

e-ISSN 2589-0042

Journal iScience

Quellenangaben Volume: 26, Issue: 11, Article Number: 108345

Publisher Elsevier

Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Lung Health and Immunity (LHI)

Grants Max Planck Society
Munich Medical & Clinician Scientist Program (MCSP)
Helmholtz Association
German Center for Lung Research