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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)
Publ. Version/Full Text DOI PMC
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
Keywords Components Of The Immune System ; Immune System ; Immunological Methods ; Proteomics; Cell Differentiation; B-cells; Lung; Identification; Pirfenidone; Prevalence; Target
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 26, Issue: 11, Pages: , Article Number: 108345 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
German Center for Lung Research (DZL)
POF-Topic(s) 30202 - Environmental Health
80000 - German Center for Lung Research
Research field(s) Lung Research
PSP Element(s) G-501693-001
G-501800-810
G-501600-004
G-501600-012
G-552100-001
Grants Max Planck Society
Munich Medical & Clinician Scientist Program (MCSP)
Helmholtz Association
German Center for Lung Research
DOI 10.1016/j.isci.2023.108345
WOS ID 001105524500001
Scopus ID 85175647168
PubMed ID 38026226
Erfassungsdatum 2023-11-28
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