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Mahendran SM, Keystone EC, Krawetz RJ, et al. Elucidating the endogenous synovial fluid proteome and peptidome of inflammatory arthritis using label-free mass spectrometry. Clin Proteomics. 2019;16:23doi: 10.1186/s12014-019-9243-3.
Mahendran, S. M., Keystone, E. C., Krawetz, R. J., Liang, K., Diamandis, E. P., & Chandran, V. (2019). Elucidating the endogenous synovial fluid proteome and peptidome of inflammatory arthritis using label-free mass spectrometry. Clinical proteomics, 1623. https://doi.org/10.1186/s12014-019-9243-3
Mahendran, Shalini M, et al. "Elucidating the endogenous synovial fluid proteome and peptidome of inflammatory arthritis using label-free mass spectrometry." Clinical proteomics vol. 16 (2019): 23. doi: https://doi.org/10.1186/s12014-019-9243-3
Mahendran SM, Keystone EC, Krawetz RJ, Liang K, Diamandis EP, Chandran V. Elucidating the endogenous synovial fluid proteome and peptidome of inflammatory arthritis using label-free mass spectrometry. Clin Proteomics. 2019 May 30;16:23. doi: 10.1186/s12014-019-9243-3. eCollection 2019. PMID: 31160890; PMCID: PMC6542032.
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Clin Proteomics. 2019 May 30;16:23. doi: 10.1186/s12014-019-9243-3. eCollection 2019.

Elucidating the endogenous synovial fluid proteome and peptidome of inflammatory arthritis using label-free mass spectrometry.

Clinical proteomics

Shalini M Mahendran, Edward C Keystone, Roman J Krawetz, Kun Liang, Eleftherios P Diamandis, Vinod Chandran

Affiliations

  1. 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada.
  2. 2Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON Canada.
  3. 3Department of Rheumatology, Mount Sinai Hospital, Toronto, ON Canada.
  4. 4McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB Canada.
  5. 5Department of Surgery, University of Calgary, Calgary, AB Canada.
  6. 6Department of Anatomy and Cell Biology, University of Calgary, Calgary, AB Canada.
  7. 7Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON Canada.
  8. 8Department of Clinical Biochemistry, University Health Network, Toronto, ON Canada.
  9. 9Centre for Prognosis Studies in Rheumatic Diseases, Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON Canada.
  10. 10Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, ON Canada.
  11. 11Institute of Medical Science, University of Toronto, Toronto, ON Canada.

PMID: 31160890 PMCID: PMC6542032 DOI: 10.1186/s12014-019-9243-3

Abstract

BACKGROUND: Inflammatory arthritis (IA) is an immunological disorder in which loss of immune tolerance to endogenous self-antigens perpetuates synovitis and eventual destruction of the underlying cartilage and bone. Pathological changes in the joint are expected to be represented by synovial fluid (SF) proteins and peptides. In the present study, a mass spectrometry-based approach was utilized for the identification of key protein and peptide mediators of IA.

METHODS: Age-matched SF samples from 10 rheumatoid arthritis patients, 10 psoriatic arthritis patients and 10 cadaveric controls were subjected to an integrated proteomic and peptidomic protocol using liquid chromatography tandem mass spectrometry. Significant differentially abundant proteins and peptides were identified between cohorts according to the results of a Mann-Whitney U test coupled to the Benjamini-Hochberg correction for multiple hypothesis testing. Fold change ratios were computed for each protein and peptide according to their log-transformed extracted ion current. Pathway analysis and antimicrobial peptide (AMP) prediction were conducted to clarify the pathophysiological relevance of identified proteins and peptides to IA.

RESULTS: We determined that 144 proteins showed significant differential abundance between the IA and control SF proteomes, of which 11 protein candidates were selected for future follow-up studies. Similar analyses applied to our peptidomic data identified 15 peptide sequences, originating from 4 protein precursors, to have significant differential abundance in IA compared to the control SF peptidome. Pathway enrichment analysis of the IA SF peptidome along with AMP prediction suggests a possible mechanistic role of microbes in eliciting an immune response which drives the development of IA.

CONCLUSIONS: The discovery-phase data generated herein has provided a basis for the identification of candidates with the greatest potential to serve as novel serum biomarkers specific to inflammatory arthritides. Moreover, these findings facilitate the understanding of possible disease mechanisms specific to each subtype.

Keywords: Biomarkers; Inflammatory arthritis; Mass spectrometry; Peptidomics; Proteomics; Psoriatic arthritis; Rheumatoid arthritis; Synovial fluid

Conflict of interest statement

Competing interestsThe authors declare that they have no competing financial interest.

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