Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Immunol Res. 2020 Nov 10;2020:2180708. doi: 10.1155/2020/2180708. eCollection 2020.
Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages' efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE.
The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients ( = 70), rheumatoid arthritis (RA) ( = 24), primary Sjögren's Syndrome (pSS) ( = 21), and healthy controls (HCs) ( = 70) using enzyme-linked immunosorbent assay (ELISA). The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence.
The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to RA, pSS, and HCs (all < 0.0001). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score ( = 0.254, = 0.034), erythrocyte sedimentation rate (ESR) ( = 0.430, < 0.001), C-reactive protein (CRP) ( = 0.246, = 0.049), and immunoglobulin G (IgG) ( = 0.408, = 0.001) and negatively associated with haemoglobin (Hb) ( = -0.294, = 0.014). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( = 0.004 and 0.044, respectively) compared with unconjugated human IgG.
These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.
系统性红斑狼疮（SLE）是一种以大量自身抗体产生为特征的疾病。巨噬细胞吞噬作用的缺陷在 SLE 的发病机制中发挥着重要作用。在巨噬细胞吞噬凋亡细胞的过程中，Tyro3 是一种负责识别凋亡细胞的受体。为了研究 Tyro3 受体在 SLE 中巨噬细胞吞噬凋亡细胞中的作用，我们旨在揭示 Tyro3 自身抗体与 SLE 的临床相关性和影响。
采用酶联免疫吸附试验（ELISA）检测新诊断、未经治疗的 SLE 患者（n=70）、类风湿关节炎（RA）（n=24）、原发性干燥综合征（pSS）（n=21）和健康对照者（HCs）（n=70）血清中针对 Tyro3 受体的 IgG 型自身抗体水平。通过流式细胞术和免疫荧光法测量来自 SLE 患者的纯化 Tyro3 自身抗体对人单核细胞衍生巨噬细胞吞噬作用的影响。
与 RA、pSS 和 HCs 相比，SLE 患者血清中针对 Tyro3 受体的 IgG 型自身抗体水平显著升高（均<0.0001）。抗-Tyro3 IgG 水平与 SLE 疾病活动指数（SLEDAI）评分呈正相关（=0.254，=0.034），与红细胞沉降率（ESR）（=0.430，<0.001）、C 反应蛋白（CRP）（=0.246，=0.049）和免疫球蛋白 G（IgG）（=0.408，=0.001）呈正相关，与血红蛋白（Hb）呈负相关（=-0.294，=0.014）。ROC 曲线表明，抗-Tyro3 抗体可将 SLE 患者与 HCs 区分开来。此外，流式细胞术和免疫荧光法表明，与未结合的人 IgG 相比，纯化的抗-Tyro3 IgG 抑制了巨噬细胞的吞噬作用（=0.004 和 0.044）。
这些观察结果表明，针对 Tyro3 的自身抗体与疾病活动相关，并可能损害巨噬细胞的吞噬作用。它可能是一种潜在的新型疾病生物标志物，并可能参与 SLE 的发病机制。
