title: Elevated serum autoantibodies against co-inhibitory PD-1 facilitate T cell proliferation and correlate with disease activity in new-onset systemic lupus erythematosus patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Junna
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Teng
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Qiongyi
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Mengru
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Juanfang
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: HaoJie
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China. winniesun2015@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China. yangchengde@hotmail.com.
authors.forename: Chengde
authors.initials: C
authors.lastname: Yang
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Autoreactive antibody; Co-inhibitor; New-onset SLE; PD-1; T cell activation