Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
Front Immunol. 2020 May 15;11:755. doi: 10.3389/fimmu.2020.00755. eCollection 2020.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, , IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154 T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA.
类风湿关节炎（RA）是一种以慢性炎症和 T 细胞过度激活为特征的自身免疫性疾病。新出现的证据表明，免疫球蛋白 D（IgD）的刺激诱导 T 细胞活化，并可能有助于疾病发病机制。在这项研究中，sIgD 浓度与 RA 患者的 28 个关节疾病活动评分（DAS28）和抗环瓜氨酸肽（抗-CCP）呈正相关。我们证明，IgD-Fc-Ig（由人 IgD Fc 结构域和 IgG Fc 结构域组成，通过原核蛋白表达和色谱纯化获得）可有效抑制健康对照者 T 细胞和 RA 患者 PBMC 中 IgD 刺激后的 T 细胞活化和增殖，恢复 Th17/Treg 细胞亚群平衡，并下调 p-Lck 和 p-ZAP70 的表达。此外，IgD-Fc-Ig 降低了胶原诱导关节炎（CIA）小鼠的肿胀关节数和关节炎指数，并改善了关节和脾脏组织的组织病理学变化。它还下调了胸腺细胞增殖，减少了辅助性 T 细胞（Th）和 CD154 T 细胞的百分比，逆转了 Th1/Th2 和 Th17/Treg 细胞亚群的失衡，降低了细胞因子和趋化因子水平，并抑制了 p-Lck 和 p-ZAP70 的表达。我们的数据表明，IgD-Fc-Ig 融合蛋白调节 RA 中的 T 细胞活性。这些发现可能对 IgD 靶向治疗 IgD 相关 RA 的策略具有重要意义。
