title: Autoantibodies to Heat-Shock Protein, HSPA5, and Epitope Spreading: High-Dose Dexamethasone Therapy Rescues Ovarian Function in Experimental Autoimmune Ovarian Insufficiency Mouse Model.
abstract: OBJECTIVE
  Role of autoantibodies to heat-shock protein 70 isoform, HSPA5, both alone or in combination with other antigenic peptides in epitope spreading and effect of high-dose dexamethasone to overcome this.
  
  
  METHODS
  Experimental autoimmune premature ovarian insufficiency mouse model generated by immunization with immunodominant epitopes of HSPA5 alone or in combination with other antigenic peptides. Two doses of dexamethasone treatment are given to the latter group. Immunosorbent assay and Western blot analysis were undertaken to detect cross-reactivity. Hormonal estimations, histological evaluation, and fertility studies were performed to assess treatment efficacy.
  
  
  RESULTS
  One of the immunodominant epitopes of HSPA5 led to epitope spreading. Of the two doses, 100 mg was more effective in rescuing fertility.
  
  
  CONCLUSIONS
  We postulate that the shared immunodominant peptide could be included in a peptide array to detect both HSAP5 and HSP90β autoantibodies for early diagnosis or prognosis of aPOI and customized glucocorticoid therapy for such subjects.
authors: Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Mumbai, India.
authors: Kaushiki M
authors: KM
authors: Kadam
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Purvi V
authors: PV
authors: Mande
authors: Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Mumbai, India.
authors: Nilesh
authors: N
authors: Gawas
authors: Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Mumbai, India.
authors: Sarika
authors: S
authors: Ahire
authors: Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Mumbai, India.
authors: Late Vrinda V
authors: LV
authors: Khole
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D003429:Cross Reactions; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D020127:Recovery of Function / Q000187:drug effects
chemical_list: D001323:Autoantibodies; D000091342:Endoplasmic Reticulum Chaperone BiP; D018841:HSP90 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C490097:Hsp90b1 protein, mouse; C000717248:Hspa5 protein, mouse; D016056:Immunodominant Epitopes; D003907:Dexamethasone
keywords: Anti-ovarian antibody; fertility; follicles; glucocorticoids; immunodominant epitopes