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

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 .