CD4 < sup > + < /sup > LAG-3 < sup > + < /sup > T Cells are Decreased in Active Psoriatic Arthritis Patients and Their Restoration In Vitro is Mediated by TNF Inhibitors

Clin Exp Immunol. 2021 Jul 26. doi: 10.1111/cei.13646. Online ahead of print.ABSTRACTPsoriatic 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 and 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 %LAG-3+ CD4+ 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-TNF or anti-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 naïve to biologics PsA patients (n = 39) as 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 pot...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Source Type: research