PXD024113

PXD024113 is an original dataset announced via ProteomeXchange.

Title	A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis (cohort 1)
Description	Rationale: The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of an underlying autoimmune disease, as present in interstitial lung diseases associated with connective tissue diseases (CTD-ILD). The prevalence of autoantibodies in IPF patients is currently unknown. Objectives: An unbiased assay for de novo discovery of autoantigens can help characterizing autoreactivities in IPF patients beyond clinically established autoimmune panels. Methods: We developed the proteomic Differential Antigen Capture (DAC) assay, capturing patient antibodies from plasma, followed by affinity purification coupled to mass spectrometry (AP-MS). The DAC assay quantifies the binding capacity of patient antibodies to proteins in a pooled native extract from lung explants (ILD explants n=41; donor controls n=12). Plasma antibodies from patients with IPF (n=35), CTD-ILD (n=24) and age-matched controls (n=32) were analyzed and validated in an independent cohort (IPF: n=40; CTD-ILD: n=20). Plasma antibody binding profiles were associated with clinical meta-data including diagnosis, lung function and transplant free survival. Measurements and Main Results: We identified 586 putative autoantigens in both study cohorts with a broad heterogeneity among disease entities and cohorts. On average, in IPF a mean±SD of 16±40 autoantigens and in CTD-ILD a mean±SD of 9±15 autoantigens were identified per patient. We identified 18 IPF-specific autoantigens validated in the second cohort. Interestingly, there was also a high number of shared autoantigens in IPF and CTD-ILD patients, with 17 being present in IPF and CTD-ILD of both cohorts. Presence of antibodies to Thrombospondin 1 (THBS1) and tubulin beta-1 chain (TUBB1) was associated with a significantly reduced survival in patients with IPF (p=0.002 and p=0.019, respectively). This signature was often associated with autoreactivity against talin-1 (TLN1), latent-transforming growth factor beta-binding protein 1 (LTBP1), epididymis secretory protein Li 112 (HEL-S-112), zyxin (ZYX), the LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1) and caldesmon (CALD1). Conclusions: Unbiased proteomic profiling reveals that the overall prevalence of autoantibodies is similar in IPF and CTD-ILD patients and identifies novel IPF specific autoantigens associated with patient survival.
HostingRepository	PRIDE
AnnounceDate	2021-02-22
AnnouncementXML	Submission_2021-02-21_23:33:49.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christoph Mayr
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-10 07:38:50	ID requested
⏵ 1	2021-02-21 23:33:49	announced

Dataset with its publication pending

submitter keyword: Lung fibrosis, IPF, CTD-ILD, autoantibodies, autoimmunity, clinical proteomics

Herbert Schiller
contact affiliation	Institute of Lung Biology and Disease and Comprehensive Pneumology Center, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, German
contact email	herbert.schiller@helmholtz-muenchen.de
lab head
Christoph Mayr
contact affiliation	CPC/ILBD HemholtzZentrum München
contact email	Christoph.Mayr@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/02/PXD024113

PRIDE project URI

• PRIDE
  1. PXD024113
     1. Label: PRIDE project
     2. Name: A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis (cohort 1)