Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis
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Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis Michael Peled,1 Marianne Strazza,1 Inbar Azoulay-Alfaguter,1 and Adam Mor1,2
Abstract—Programmed death-1 (PD-1) is an inhibitory co-receptor that is highly expressed in T lymphocytes that has been shown to downregulate inflammatory responses in several inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis. Yet, the role of PD-1 in psoriatic arthritis (PsA) has not been studied. In order to fill this gap, we measured the expression levels of PD-1 in peripheral T cells from patients with active disease. Twenty patients and fifteen age-matched healthy control subjects were recruited. The percentage of CD3+PD-1+ T cells was measured by flow cytometry. Despite normal concentration of peripheral T cells, the expression levels of PD-1 were significantly higher in patients compared to healthy controls. Interestingly, among the patients, the expression levels inversely correlated with disease activity measured by disease activity scores (DAS28). PD-1 expression levels strongly correlated with the number of tender and swollen joints, but not with Creactive protein (CRP) levels or psoriasis area and severity index (PASI). Functionally, in vitro ligation of PD-1 receptor in PsA T cells inhibited interleukin-2 (IL-2) secretion, Akt phosphorylation, and Rap1 activation. These findings suggest that PD-1 might serve as a biomarker for disease activity in PsA and highlight the need for additional studies in order to establish the role of PD-1 in PsA pathogenesis. KEY WORDS: psoriatic arthritis; PD-1; signaling.
INTRODUCTION Psoriatic arthritis (PsA) is an inflammatory arthritis that develops in 30 % of patients who have cutaneous psoriasis [1–3]. These patients suffer from synovitis, tendinitis, enthesitis, dactylitis, onycholysis, and spondylitis. Prolonged inflammation leads to extensive joint damage, and therefore, early diagnosis and treatment is mandatory. T lymphocytes (T cells) play a key role in the pathogenesis of both psoriasis and PsA [4]. Activated T cells infiltrate the skin and stimulate keratinocytes to proliferate and produce interleukin-2 (IL-2) and other growth factors. Activated T cells also overexpress CD80, a co-stimulatory receptor, suggesting that co-stimulation contributes to dermal T cell activity [5, 6]. T cells from synovial fluid of New York University Clinical and Translational Science Institute and the American College of Rheumatology supported this study. 1
The Department of Medicine, New York University School of Medicine, 450 E 29th Street, New York, NY 10016, USA 2 To whom correspondence should be addressed at The Department of Medicine, New York University School of Medicine, 450 E 29th Street, New York, NY 10016, USA. E-mail: [email protected]
patients with PsA have an activated phenotype and drugs that target T cells, such as cyclosporine and alefacept (LFA3/Fc), have demonstrated beneficial effects both in skin and joint manifestations [7]. During antigen presentation, T cells require at lea
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