title: A new type of natural bispecific antibody with potential protective effect in Hashimoto thyroiditis.
abstract: BACKGROUND
  As a new antibody concept, natural bispecific antibodies (nBsAbs) have been detected in long-term passive immunization and some diseases, but their potential immunomodulatory role remains unclear. Hashimoto thyroiditis (HT) appears to fulfill the condition for nBsAb production but has not yet been characterized.
  
  
  OBJECTIVE
  The objective of the study was to identify a new nBsAb against thyroid peroxidase (TPO) and thyroglobulin (Tg) in HT patients and to preliminarily explore its immunomodulatory role.
  
  
  METHODS
  Serum samples were obtained from 136 HT patients, 92 diseased controls, and 99 healthy controls for anti-TPO/Tg nBsAb detection. The relationship between anti-TPO/Tg nBsAb and other clinical parameters was also analyzed.
  
  
  METHODS
  The anti-TPO/Tg nBsAb was detected using a double-antigen sandwich ELISA. Higher nBsAb levels were found to be associated with decreased inflammation in HT patients.
  
  
  RESULTS
  The prevalence of anti-TPO/Tg nBsAb in HT was 44.9% (61 of 136), significantly higher than that of diseased controls (2.2%, 2 of 92) (P < .0001) and healthy controls (0%, 0 of 99) (P < .0001). HT patients who were nBsAb positive were prone to have significantly lower levels of serum C-reactive protein and TNF-α compared with the nBsAb-negative individuals (P < .05). The serum amyloid A and interferon-γ levels also showed a similar trend in the two groups. The IgG subclass of anti-TPO/Tg nBsAb was IgG4. Further analysis showed a negative correlation between anti-TPO/Tg nBsAb and serum total IgG4 (r = -0.697, P = .025) in IgG4 thyroiditis patients.
  
  
  CONCLUSIONS
  A new type of nBsAb against TPO and Tg in HT patients is identified. Our data also indicate a protective effect of anti-TPO/Tg nBsAb in the pathogenesis of HT and extend prior knowledge about nBsAb in diseases.
authors.affiliation: National Center for Clinical Laboratories (W.L., G.F., L.C., R.Z., K.Z., Y.S., G.L., J.X., L.W., J.L.), Beijing Hospital, Beijing 100029, People's Republic of China; and Graduate School (W.L., G.F., L.C.), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, People's Republic of China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Li
authors.forename: Gaowei
authors.initials: G
authors.lastname: Fan
authors.forename: Lida
authors.initials: L
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Guigao
authors.initials: G
authors.lastname: Lin
authors.forename: Jiehong
authors.initials: J
authors.lastname: Xie
authors.forename: Lunan
authors.initials: L
authors.lastname: Wang
authors.forename: Jinming
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification; D001667:Binding, Competitive / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050031:Hashimoto Disease / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D007167:Immunotherapy / Q000379:methods; D007453:Iodide Peroxidase / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D013954:Thyroglobulin / Q000276:immunology*; D055815:Young Adult
chemical_list: D018033:Antibodies, Bispecific; D001323:Autoantibodies; D007074:Immunoglobulin G; D013954:Thyroglobulin; D007453:Iodide Peroxidase