Interleukin‐17+CD8+ T Cells Are Enriched in the Joints of Patients With Psoriatic Arthritis and Correlate With Disease Activity and Joint Damage Progression

Abstract

ObjectivePsoriatic 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.MethodsMononuclear 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.ResultsWithin 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 (P = 0.0003 and P = 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 (P = 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, P = 0.01), ESR (r = 0.59, P = 0.004), and DAS28 (r = 0.52, P = 0.01), and was increased in patients with erosive disease (P < 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, P = 0.04).ConclusionThese 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.

Secukinumab: A New Treatment Option for Psoriatic Arthritis

“…T cells express IL-17A, IL-17A-producing CD8 ? T cells are more abundant in the synovial fluid of patients with PsA, compared to healthy individuals, and the levels of these cells positively correlate with measures of disease activity and joint damage progression [33] Fig. 1) [29,[36][37][38][39].…”

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

“…This, of course, disregards the specificity of the TCR, the developmental relationship between the subsets, and many differences are not noted here. For instance, the type‐17 master transcription factor ROR γ t is expressed by MAIT cells11, 128 as well as non‐MAIT CD8+ T‐cells under inflammatory conditions,132, 133 but not in NK cells. However, the general inverse correlation between cytokine responsiveness and responsiveness to activating receptors may in part explain the functional similarities between CD8+ T‐cell and NK cell subsets.…”

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial

“…[11][12][13][14][15] IL-17A can mediate a variety of effector biologic functions that can result in joint and enthesial inflammation, damage, and tissue remodeling. 16 Secukinumab, a human, monoclonal antibody that inhibits the effector function of IL-17A, has been shown to be superior to placebo and etanercept in improving psoriasis signs and symptoms.…”