title: A Cytomegalovirus Peptide-Specific Antibody Alters Natural Killer Cell Homeostasis and Is Shared in Several Autoimmune Diseases.
abstract: Human cytomegalovirus (hCMV), a ubiquitous beta-herpesvirus, has been associated with several autoimmune diseases. However, the direct role of hCMV in inducing autoimmune disorders remains unclear. Here we report the identification of an autoantibody that recognizes a group of peptides with a conserved motif matching the Pp150 protein of hCMV (anti-Pp150) and is shared among patients with various autoimmune diseases. Anti-Pp150 also recognizes the single-pass membrane protein CIP2A and induces the death of CD56(bright) NK cells, a natural killer cell subset whose expansion is correlated with autoimmune disease. Consistent with this finding, the percentage of circulating CD56(bright) NK cells is reduced in patients with several autoimmune diseases and negatively correlates with anti-Pp150 concentration. CD56(bright) NK cell death occurs via both antibody- and complement-dependent cytotoxicity. Our findings reveal that a shared hCMV-induced autoantibody is involved in the decrease of CD56(bright) NK cells and may thus contribute to the onset of autoimmune disorders.
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Mu
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Gao
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: He-Qiu
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Immunology, Peking University, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Beijing Institute of Transfusion Medicine, Beijing 100850, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China. Electronic address: yangg62033@outlook.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, People's Hospital, Peking University, Beijing 100044, China. Electronic address: zgli99@aliyun.com.
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Li
mesh_terms: D000914:Antibodies, Viral / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000276:immunology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D014764:Viral Proteins