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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Arthritis Research & Therapy 1/2017

Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients

Zeitschrift:
Arthritis Research & Therapy > Ausgabe 1/2017
Autoren:
Hui Shi, Junna Ye, Jialin Teng, Yufeng Yin, Qiongyi Hu, Xinyao Wu, Honglei Liu, Xiaobing Cheng, Yutong Su, Mengru Liu, Juanfang Gu, Ting Lu, HaoJie Chen, Hui Zheng, Yue Sun, Chengde Yang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13075-017-1258-4) contains supplementary material, which is available to authorized users.

Abstract

Background

Programmed 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.

Methods

Serum 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.

Results

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), 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).

Conclusions

The 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.
Zusatzmaterial
Additional file 1: Figure S1. Serum levels of anti-PD-1 IgG in new-onset SLE patients classified into four equal groups according to the SLEDAI score. Values represent the means ± SD. ***p < 0.001. **p < 0.01. *p < 0.05. ns no significance. (TIF 402 kb)
13075_2017_1258_MOESM1_ESM.tif
Literatur
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