title: Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus.
abstract: OBJECTIVE
  Estrogens influence many physiologic processes and are also implicated in the development or progression of numerous diseases, including autoimmune disorders. Aberrations of lymphocyte homeostasis that lead to the production of multiple pathogenic autoantibodies, including autoantibodies specific to estrogen receptor (ER), have been detected in the peripheral blood of patients with systemic lupus erythematosus (SLE). This study was undertaken to assess the presence of both anti-ERα and anti-ERβ antibodies in sera from patients with SLE, to analyze the effect of these antibodies on peripheral blood T lymphocyte homeostasis, and to evaluate their role as determinants of disease pathogenesis and progression.
  
  
  METHODS
  Anti-ER antibody serum immunoreactivity was analyzed by enzyme-linked immunosorbent assay in samples from 86 patients with SLE and 95 healthy donors. Phenotypic and functional analyses were performed by flow cytometry and Western blotting.
  
  
  RESULTS
  Anti-ERα antibodies were present in 45% of the patients with SLE, whereas anti-ERβ antibodies were undetectable. In healthy donors, anti-ERα antibodies induced cell activation and consequent apoptotic cell death in resting lymphocytes as well as proliferation of anti-CD3-stimulated T lymphocytes. A significant association between anti-ERα antibody values and clinical parameters, i.e., the SLE Disease Activity Index and arthritis, was found.
  
  
  CONCLUSIONS
  Our data suggest that anti-ERα autoantibodies interfere with T lymphocyte homeostasis and are significantly associated with lupus disease activity.
authors.affiliation: Istituto Superiore di Sanità, Rome, Italy, and San Raffaele Institute Sulmona, L'Aquila, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Colasanti
authors.forename: Angela
authors.initials: A
authors.lastname: Maselli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbati
authors.forename: Davide
authors.initials: D
authors.lastname: Vacirca
authors.forename: Antonella
authors.initials: A
authors.lastname: Tinari
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiarotti
authors.forename: Antonello
authors.initials: A
authors.lastname: Giovannetti
authors.forename: Flavia
authors.initials: F
authors.lastname: Franconi
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001528:Behcet Syndrome / Q000097:blood / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha / Q000276:immunology*; D047629:Estrogen Receptor beta / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C479998:estrogen receptor beta isoform M, human