title: Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate Primary Sjögren's Syndrome.
abstract: OBJECTIVE
  Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS.
  
  
  METHODS
  BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA.
  
  
  RESULTS
  Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls.
  
  
  CONCLUSIONS
  Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis.
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.|Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Qiaoniang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Deng
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Renliang
authors.initials: R
authors.lastname: Huang
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Rheumatology of the First Afflict Hospital of Xiamen University, Xiamen, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Rheumatology of the First Afflict Hospital of Xiamen University, Xiamen, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Clinical laboratory, Xiamen University Hospital, Xiamen University, Xiamen, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Xiamen, China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Priority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Petersen
authors.affiliation: Laboratory of Autoimmunity, Medical College of Xiamen University, Xiamen, China.|Priority Area Asthma & Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D017433:Protein Structure, Secondary; D043587:Receptor, Muscarinic M3 / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D043587:Receptor, Muscarinic M3