ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1586

Quantitative Proteomic Analysis of Synovial Fluid and Skin Identifies Putative Psoriatic Arthritis Biomarkers

Daniela Cretu1, Kun Liang2, Dafna D. Gladman3, Eleftherios Diamandis4 and Vinod Chandran3, 1Laboratory Medicine and Pathobiology, Unviersity of Toronto, Mount Sinai Hospital, Ontario, Canada, Toronto, ON, Canada, 2Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada, 3University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 4Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Spondyloarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment II

Session Type: Abstract Submissions (ACR)

Background/Purpose

Psoriatic arthritis (PsA) is a unique form of arthritis occurring in 30% of psoriasis patients. There is a high prevalence of undiagnosed PsA in psoriasis patients; therefore identifying soluble biomarkers for PsA will help in screening psoriasis patients for appropriate referral to a rheumatologist. Potential PsA biomarkers likely originate in sites of inflammation, such as inflamed joints and skin, and subsequently enter systemic circulation. We hypothesize that quantitative proteomic analysis of synovial fluid (SF) and skin obtained from PsA patients, willgenerate a comprehensive list of proteins specific to PsA, facilitating the identification of potential PsA screening biomarkers.

Methods

SF was obtained from swollen knee joints of 10 PsA patients, and age/sex matched early osteoarthritis (OA) controls. Likewise, skin biopsies were obtained from involved and uninvolved skin of 10 PsA, and 10 age/sex matched psoriasis patients. Using strong cation exchange chromatography, followed by tandem mass spectrometry, we characterized the proteomes of pooled SF and pooled skin samples. Extracted ion current (XIC) intensities were used to calculate protein abundance ratios, and utilized to classify upregulated proteins. Selected reaction monitoring (SRM) assays were developed to quantify these potential PsA markers in individual patient samples. Identified markers were subsequently measured in serum samples from 33 PsA and 15 PsC patients, using commercially available or in-house developed enzyme-linked immunosorbent assays (ELISA).

Results

We quantified a total of 443 and 1922 proteins in SF and skin extracts, respectively, but only 17 proteins represented upregulated proteins in PsA SF, while 47 proteins were specifically elevated in PsA-derived skin. SRM validation confirmed that 12 and 8 proteins were indeed elevated in an independent set of PsA SF and involved PsA skin, respectively. Based on the fold change between PsA and controls, the associated P-values, and the cellular localization, we ranked the proteins, and selected the following putative markers for validation in the serum – S100A9, M2BP, CD5L, MMP3, CRP, EPO, POSTN, and ITGB5. Only ITGB5, (1.2±0.5 compared to 0.8±0.6; P=0.007), M2BP (553.0±150.9 compared to 453.0±115.0; P=0.027), EPO (19.6±12.3 compared to 13.7±12.2;P=0.035), and MMP3 (3.4±3.4 compared to 1.8±1.1; P=0.046) were significantly elevated in PsA serum compared to PsC.

Conclusion

Proteomic analysis of PsA SF and skin has identified 20 candidate biomarkers, and 4 of these have been confirmed in serum following a small-scale validation. In the future, these markers must be validated in a larger and independent sample cohort, in order to identify their clinical utility in PsA patients. Additionally, these proteins may also uncover aspects of PsA pathobiology that are currently unknown.

Disclosure:

D. Cretu,
None;

K. Liang,
None;

D. D. Gladman,

AbbVie Canada,

5;

E. Diamandis,
None;

V. Chandran,

AbbVie ,

5.

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