CD4+ LAG-3+ T cells are decreased in active psoriatic arthritis patients and their restoration in vitro is mediated by TNF inhibitors

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with T cell dysregulation. The lymphocyte-activation gene (LAG)-3 is one of the regulatory receptors expressed on T cells in a soluble form. LAG-3 expression on T cells was analyzed in vitro in PsA patients with minimal disease activity (MDA), active disease (non-MDA) and healthy controls. In cultured in-vitro peripheral blood mononuclear cells (PBMCs), LAG-3 expression on CD4⁺ T cells was similar in both MDA PsA patients (7.5 ± 0.9) (n = 14) and healthy controls (7.8 ± 0.6) (n = 15), but significantly lower in non-MDA PsA patients (3.1 ± 0.3) (n = 13) (p < 0.0001). An inverse correlation between PsA clinical disease activity and %CD4⁺ LAG-3⁺ T cells in vitro was observed (composite psoriatic disease activity index r = -0.47, p < 0.02 and psoriatic arthritis disease activity score, r = -0.51, p < 0.008). In-vitro co-culture of CD4⁺ T cells with anti-tumor necrosis factor (TNF) or anti-interleukin (IL)-17A had no effect on LAG-3⁺ expression in MDA PsA patients and healthy controls. In non-MDA patients, anti-TNF, but not anti-IL-17A, restored the %CD4⁺ LAG-3⁺ T cells (7.9 ± 0.9 and 3.2 ± 0.4, respectively) (p < 0.0004). Lower soluble LAG-3 levels were found in sera of naive to biological PsA patients (n = 39) compared to healthy controls (n = 35) (p < 0.03). Impaired LAG-3 on CD4⁺ T cells may reflect active PsA disease state. Anti-TNFs have potency to up-regulate the CD4⁺ LAG-3⁺ T cells in vitro.

Keywords: T cells; arthritis (including rheumatoid arthritis); inhibitory/activating receptors.