Dataset Information

Hs_PanLibrary_CAL51

ABSTRACT: Hs_PanLibrary_CAL51

REANALYSIS of: PXD000953

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Others

SUBMITTER: Rosenberger G, et al.

PROVIDER: PAe005346 | PeptideAtlas | 2014-12-31

REPOSITORIES: PeptideAtlas

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Publications

A repository of assays to quantify 10,000 human proteins by SWATH-MS.

Rosenberger George G Koh Ching Chiek CC Guo Tiannan T Röst Hannes L HL Kouvonen Petri P Collins Ben C BC Heusel Moritz M Liu Yansheng Y Caron Etienne E Vichalkovski Anton A Faini Marco M Schubert Olga T OT Faridi Pouya P Ebhardt H Alexander HA Matondo Mariette M Lam Henry H Bader Samuel L SL Campbell David S DS Deutsch Eric W EW Moritz Robert L RL Tate Stephen S Aebersold Ruedi R

Scientific data 20140916

Mass spectrometry is the method of choice for deep and reliable exploration of the (human) proteome. Targeted mass spectrometry reliably detects and quantifies pre-determined sets of proteins in a complex biological matrix and is used in studies that rely on the quantitatively accurate and reproducible measurement of proteins across multiple samples. It requires the one-time, a priori generation of a specific measurement assay for each targeted protein. SWATH-MS is a mass spectrometric method th ...[more]

PMID: 25977788

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Project description:Rheumatoid arthritis is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.

Dataset Information

Hs_PanLibrary_CAL51

Publications

A repository of assays to quantify 10,000 human proteins by SWATH-MS.

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