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.

中文翻译：

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活动性银屑病关节炎患者的 CD4+LAG-3+ T 细胞减少，其体外恢复由 TNF 抑制剂介导

银屑病关节炎 (PsA) 是一种与 T 细胞失调相关的慢性炎症性疾病。淋巴细胞激活基因 (LAG)-3 是 T 细胞上以可溶形式表达的调节受体之一。在具有最小疾病活动性（MDA）、活动性疾病（非MDA）和健康对照的 PsA 患者中体外分析 T 细胞上的 LAG-3 表达。在体外培养的外周血单核细胞 (PBMC) 中，^MDA PsA 患者 (7.5 ± 0.9) ( n  = 14) 和健康对照 (7.8 ± 0.6) ( n  = 15)，但在非 MDA PsA 患者中显着较低 (3.1 ± 0.3) ( n  = 13) ( p  < 0.0001)。体外观察到 PsA 临床疾病活动度与 %CD4 ⁺ LAG-3 ⁺ T 细胞之间呈负相关（复合银屑病疾病活动指数r  = -0.47，p  < 0.02 和银屑病关节炎疾病活动评分，r  = -0.51，p  < 0.008）。CD4 ⁺ T 细胞与抗肿瘤坏死因子 (TNF) 或抗白细胞介素 (IL)-17A 的体外共培养对MDA PsA 患者和健康对照中的LAG-3 ^{+表达没有影响。}在非 MDA 患者中，抗 TNF（而非抗 IL-17A）恢复了 %CD4 ⁺ LAG-3 ⁺ T 细胞（分别为 7.9 ± 0.9 和 3.2 ± 0.4）（p  < 0.0004）。与健康对照 ( n  = 35) 相比，首次接触生物性 PsA 患者 ( n  = 39) 的血清中可溶性 LAG-3 水平较低 ( p  < 0.03)。^{CD4 +} T 细胞上的 LAG-3 受损可能反映活动性 PsA 疾病状态。抗 TNF 能够在体外上调 CD4 ⁺ LAG-3 ⁺ T 细胞。