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Where to Stand with Stromal Cells and Chronic Synovitis in Rheumatoid Arthritis?
Open AccessArticle

Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activity of Synovial Fibroblasts

1
University College Dublin Centre for Arthritis Research, Conway Institute, University College Dublin, Dublin D04 W6F6, Ireland
2
Molecular Rheumatology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D06 R590, Ireland
*
Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1300; https://doi.org/10.3390/cells8101300
Received: 19 August 2019 / Revised: 18 October 2019 / Accepted: 21 October 2019 / Published: 22 October 2019
(This article belongs to the Special Issue The Molecular and Cellular Basis for Rheumatoid Arthritis)
rs26232, located in intron one of C5orf30, is associated with the susceptibility to and severity of rheumatoid arthritis (RA). Here, we investigate the relationship between this variant and the biological activities of rheumatoid arthritis synovial fibroblasts (RASFs). RASFs were isolated from the knee joints of 33 RA patients. The rs26232 genotype was determined and cellular migration, invasion, and apoptosis were compared using in vitro techniques. The production of adhesion molecules, chemokines, and proteases was measured by ELISA or flow cytometry. Cohort genotypes were CC n = 16; CT n = 14; TT n = 3. In comparison with the RASFs of the CT genotype, the CC genotype showed a 1.48-fold greater invasiveness in vitro (p = 0.02), 1.6-fold higher expression intracellular adhesion molecule (ICAM)-1 (p = 0.001), and 5-fold IFN-γ inducible protein-10 (IP-10) (p = 0.01). There was no association of the rs26232 genotype with the expression levels of either total C5orf30 mRNA or any of the three transcript variants. The rs26232 C allele, which has previously been associated with both the risk and severity of RA, is associated with greater invasive activity of RASFs in vitro, and with higher expression of ICAM-1 and IP-10. In resting RASFs, rs26232 is not a quantitative trait locus for C5orf30 mRNA, indicating a more complex mechanism underlying the genotype‒phenotype relationship. View Full-Text
Keywords: rheumatoid arthritis; synovium; fibroblasts; genetics; C5orf30; genotype‒phenotype rheumatoid arthritis; synovium; fibroblasts; genetics; C5orf30; genotype‒phenotype
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MDPI and ACS Style

Dorris, E.R; Linehan, E.; Trenkmann, M.; Veale, D.J; Fearon, U.; Wilson, A.G. Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activity of Synovial Fibroblasts. Cells 2019, 8, 1300. https://doi.org/10.3390/cells8101300

AMA Style

Dorris ER, Linehan E, Trenkmann M, Veale DJ, Fearon U, Wilson AG. Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activity of Synovial Fibroblasts. Cells. 2019; 8(10):1300. https://doi.org/10.3390/cells8101300

Chicago/Turabian Style

Dorris, Emma R; Linehan, Eimear; Trenkmann, Michelle; Veale, Douglas J; Fearon, Ursula; Wilson, Anthony G. 2019. "Association of the Rheumatoid Arthritis Severity Variant rs26232 with the Invasive Activity of Synovial Fibroblasts" Cells 8, no. 10: 1300. https://doi.org/10.3390/cells8101300

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