Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients.
Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients.
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针对共抑制性 PD-1 的血清自身抗体升高促进 T 细胞增殖并与新发系统性红斑狼疮患者的疾病活动相关
DOI：
10.1186/s13075-017-1258-4
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发表时间：
2017-03-09
影响因子：
4.9
通讯作者：
Yang C
中科院分区：
文献类型：
--
作者：
Shi H;Ye J;Teng J;Yin Y;Hu Q;Wu X;Liu H;Cheng X;Su Y;Liu M;Gu J;Lu T;Chen H;Zheng H;Sun Y;Yang C
程序性死亡蛋白1（PD-1）在T细胞激活过程中作为一种抑制性信号在免疫响应调节中起着重要作用，但是，对于全身性狼疮的血清自动抗体曲线（SLE）的血清自动抗体特征（SLE）是一种疾病（SLE） D-1患者新的SLE。
在新发作的SLE患者（n = 90），类风湿关节炎（n = 50），原发性Sjogren的综合征（n = 50），链球菌炎（n = 25）和健康对照（n = 80）中，抗PD-1 IgG和IgM同种型的水平被检测-pd-1具有临床特征和实验室参数分析了新的SLE，使用流式细胞仪测量了SLE患者纯化的抗PD-1 IgG对T细胞增殖的影响。
The data revealed increased levels of anti-PD-1 IgG, but not IgM, especially in new-onset SLE patients, and the positive rate of anti-PD-1 IgG was 30 (33.3%). The level of anti-PD-1 IgG was closely associated with malar rash (OR=15.773), arthritis (OR=22.937), serasitis (OR=16.008), hematological (OR=35.187), renal (OR=8.306), and neurological involvement （OR = 37.282）。与树突状细胞（DCS）共培养时。
当前的研究首次表明，针对PD-1的共抑制剂自身抗体的血清水平在新的SLE患者中升高，并且与SLE的疾病活性相关。
本文的在线版本（DOI：10.1186/S13075-017-1258-4）包含补充材料，可供授权用户使用。
BackgroundProgrammed cell death protein 1 (PD-1) plays an important role in immune response regulation as a co-inhibitory signal during T cell activation. However, there is little known about the serum autoantibody profile of PD-1 in systemic lupus erythematosus (SLE), a disease characterized by the breakdown of immune tolerance to self-antigens and an excessive production of autoantibodies. Thus, we aim to investigate the serum levels and function of anti-PD-1 in patients with new-onset SLE.MethodsSerum levels of anti-PD-1 IgG and IgM isotypes were detected in new-onset SLE patients (n= 90), rheumatoid arthritis (n= 50), primary Sjogren’s syndrome (n= 50), ankylosing spondylitis (n= 25), and healthy controls (HC) (n= 80) using an enzyme-linked immunosorbent assay (ELISA). The correlation of anti-PD-1 with clinical characteristics and laboratory parameters of patients with new-onset SLE was analyzed. The effects of purified anti-PD-1 IgG from SLE patients on T cell proliferation were measured using flow cytometry.ResultsThe data revealed increased levels of anti-PD-1 IgG, but not IgM, especially in new-onset SLE patients, and the positive rate of anti-PD-1 IgG was 30 (33.3%). The level of anti-PD-1 IgG was closely associated with malar rash (OR = 15.773), arthritis (OR = 22.937), serositis (OR = 16.008), hematological (OR = 35.187), renal (OR = 8.306), and neurological involvement (OR = 37.282). Moreover, the serum levels of anti-PD-1 IgG were positively correlated with the SLE disease activity index (SLEDAI) score (r = 0.296,p= 0.0046) and the erythrocyte sedimentation rate (ESR) (r = 0.2446,p= 0.0201). In vitro examination showed that purified anti-PD-1 IgG obtained from SLE patients enhanced T cell proliferation when co-cultured with dendritic cells (DCs).ConclusionsThe current study indicates, for the first time, that the serum levels of co-inhibitor autoantibodies against PD-1 are elevated in new-onset SLE patients and are associated with disease activity in SLE. Autoantibodies against PD-1, facilitating T cell proliferation, revealed a new insight into the function of negative regulation signals involved in the pathogenesis of SLE.