Background Syndecans includes a group of proteins from the cell-surface heparan-sulfate proteoglycan family, with a relevant role in chronic inflammation of synovial tissue in patients with rheumatoid arthritis (RA) participating in the cell-matrix and cell-cell interactions. Syndecans are differentially expressed in the synovial tissue: syndecan-1 (SDC-1) is expressed mainly in mononuclear cells, syndecan-3 (SDC-3) is mainly expressed by synovial endothelial cells and syndecan-4 (SDC-4) is expressed by B lymphocytes regulating B cell development and survival. Currently, there is strong evidence that antibodies directed to citrullinated protein antigens (ACPAs) are associated with a more severe disease in RA. Nevertheless, to date, there is a lack of information about the relation between serum syndecan levels and serum concentrations of rheumatoid factor (RF) and ACPAs.

Objectives To evaluate the association between serum SDC-1, SDC-3 and SDC-4 levels with serum concentrations of RF and ACPAs.

Methods Eighty-one, patients with RA were included. We assessed clinical characteristics including disease activity by DAS-28, functioning by HAQ-Di. Serum concentrations of RF were measured by nephelometry, two ACPAs were measured: anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV) antibodies using ELISA. Serum levels of SDC-1, SDC-3 (ng/mL) and SDC-4 (pg/mL) were measured by ELISA. We compared the serum levels of these syndecans in the ACPA+ group (group 1) versus ACPA- group (group 2) with Student t-test. A correlation analysis (Pearson tests) was performed to identify the strength of association between concentrations of syndecans with concentrations of ACPAs and other variables.

Results Patients with RA had a mean age of 50±11 yrs, 75% were RF+ and 64% were ACPA+. In patients with ACPAs+ were observed higher serum concentrations of SDC-3 (p=0.003) and SDC-4 (p<0.001). SDC-1 correlated significantly with anti-MCV (r=0.53, p<0.001). Serum concentrations of SDC-3 correlated significantly with anti-CCP titres (r=0.53, p=0.003) and anti-MCV (r=0.46, p=0.02); whereas SDC-4 levels correlated significantly with anti-CCP titres (r=0.61, p<0.001) and RF (r=0.53, p=0.003). Additionally, serum SDC-1 levels correlated with decrement in response to treatment with synthetic DMARDs (r=-0.25, p=0.026). SDC-1 did not correlate with serum SDC-3 (p=0.8) and SDC-4 (p=0.8); whereas serum SDC-3 and SDC-4 had a strong correlation (r=0.8, p<0.001).

Conclusions Serum SDC-3 and SDC-4 are increased in ACPA-positive RA patients. These data suggest that syndecans might be useful as serum biomarkers for discriminate a group of patients with RA and more severe disease.

References

1. Patterson AM, et al. Ann Rheum Dis. 2008 May;67(5):592–601.

2. Endo T, et al. Arthritis Rheumatol. 2015 Sep;67(9):2512–22.

References

Acknowledgements This project was supported by a grant from the Fondo de Investigacion en Salud del Instituto Mexicano del Seguro Social: FIS/IMSS/PROT/G15/1448.

Disclosure of Interest N. Rodriguez-Jimenez: None declared, E. Cardona-Muñoz: None declared, J. Gamez-Nava: None declared, E. Perez-Guerrero: None declared, M. Ponce-Guarneros: None declared, E. Vera-Navarrete: None declared, A. Nava-Zavala: None declared, T. Garcia-Cobian: None declared, M. Salazar-Paramo: None declared, L. Gonzalez-Lopez Grant/research support from: Dr. L Gonzalez-Lopez is a recipient of a Fundacion IMSS Scholarship, Mexico.