Interleukin‐17+CD8+ T Cells Are Enriched in the Joints of Patients With Psoriatic Arthritis and Correlate With Disease Activity and Joint Damage Progression1. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Menon, Bina; Gullick, Nicola J.; Walter, Gina J.; Rajasekhar, Megha; Garrood, Toby; Evans, Hayley G.; Taams, Leonie S.; Kirkham, Bruce W.
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 5(2014)
• Page Start: 1272
• Page End: 1281
• Publication Date: 2014-05
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38376
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38376-sec-0001" sec-type="section"> <title>Objective</title> <p>Psoriatic arthritis (PsA) is associated with HLA class I genes, in contrast to the association with HLA class II in rheumatoid arthritis (RA). Since IL‐17+ cells are considered important mediators of synovial inflammation, we sought to determine whether IL‐17–producing CD8+ T cells may be found in the joints of patients with PsA and whether these cells might contribute to the disease process.</p> </sec> <sec id="art38376-sec-0002" sec-type="section"> <title>Methods</title> <p>Mononuclear cells from paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with PsA or patients with RA were stimulated ex vivo, and CD4− T cells were examined by flow cytometry for cytokine expression, cytotoxic markers, and frequencies of γ/δ or mucosal‐associated invariant T cells. Clinical measures of arthritis activity (C‐reactive protein [CRP] level, erythrocyte sedimentation rate [ESR], Disease Activity Score in 28 joints [DAS28]) and power Doppler ultrasound (PDUS) scores for the presence of active synovitis in the aspirated knee were recorded and assessed for correlations with immunologic markers.</p> </sec> <sec id="art38376-sec-0003" sec-type="section"> <title>Results</title> <p>Within the CD3+ T cell compartment, both IL‐17+CD4− (predominantly CD8+) and IL‐17+CD4+ T cells were significantly enhanced in the SF compared to the PB of patients with PsA (<italic>P</italic> = 0.0003 and <italic>P</italic> = 0.002, respectively; n = 21), whereas in patients with RA, only IL‐17+CD4+ T cells were increased in the SF compared to the PB (<italic>P</italic> = 0.008; n = 14). The frequency of IL‐17+CD4− T cells in PsA SF was positively correlated with the CRP level (r = 0.52, <italic>P</italic> = 0.01), ESR (r = 0.59, <italic>P</italic> = 0.004), and DAS28 (r = 0.52, <italic>P</italic> = 0.01), and was increased in patients with erosive disease (<italic>P</italic> < 0.05). In addition, the frequency of IL‐17+CD4− T cells positively correlated with the PDUS score, a marker for active synovitis (r = 0.49, <italic>P</italic> = 0.04).</p> </sec> <sec id="art38376-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These results show, for the first time, that the PsA joint, but not the RA joint, is enriched for IL‐17+CD8+ T cells. Moreover, the findings reveal that the levels of this T cell subset are correlated with disease activity measures and the radiographic erosion status after 2 years, suggesting a previously unrecognized contribution of these cells to the pathogenesis of PsA.</p> </sec> </abstract>