Analysis of Programmed Death-1 in Patients with Psoriatic Arthritis

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 C-reactive 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.

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells

“…Furthermore, another recent study also reported increased PD-1 expression on PBMCs in patients with psoriatic arthritis. 33 Taken together, these data indicate that PD-1 is overexpressed on T cells not only in the mouse model of psoriasis but also in patients with psoriasis, underscoring the promise of the PD-L1 protein as a therapy for patients with psoriasis. However, an important difference between IL-17A-producing T cells in the mouse model and human patients with psoriasis needs to be noted.…”

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis

“…However, the co-IR expression patterns on various lymphocyte subsets show considerable disease-dependent variation. For example, PD-1 is increased in CD4 + and CD8 + T and NK cells from lupus patients (36,37), and in CD3 + T cells from psoriatic arthritis patients (38), while in SSc it is only significantly enhanced in Tregs and γδ T cells (Fig. 1C).…”

Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases

“…3). Unlike RA T cells, however, PsA T cells exhibit increased signalling through the AKT– mTOR axis 148 ; this observation may result from increased expression of programmed death-1 (PD-1) in T cells from patients with PsA 148 .…”