CD4+LAG-3+ T cells are decreased in active psoriatic arthritis patients and their restorationin vitrois 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.

Role of co‑inhibitory molecules in the treatment of psoriasis (Review)

“…A previous study revealed an inverse association between the PASI score and the level of CD4+CD49b+LAG-3+Type 1 Tregs in the blood of patients with psoriasis (53). Reduced LAG-3 levels were also found in patients with PsA (54). For psoriasis, the production of interferon (IFN)a by plasmacytoid DCs is the initial event in the innate cascade to pathologic inflammation.…”

Psoriatic arthritis: one year in review 2022

“…was associated with impaired levels of lymphocyte-activation gene (LAG)-3 receptor expression on CD4 + lymphocytes. The authors also noted TNF inhibitors (TNFi) could up-regulate CD4-LAG-3+ levels, with possible improvement on the control of disease activity (12). Considering that phosphodiesterase 4 (PDE4) could be involved in the cleavage of the soluble form of CD40L (sCD40L), a second study by Venerito et al investigated the effect of Apremilast (APR), a PDE4 inhibitor, on sCD40L levels and PsA activity.…”