Autoantibodies to Heat-Shock Protein, HSPA5, and Epitope Spreading: High-Dose Dexamethasone Therapy Rescues Ovarian Function in Experimental Autoimmune Ovarian Insufficiency Mouse Model

Am J Reprod Immunol. 2016 May;75(5):580-93. doi: 10.1111/aji.12494. Epub 2016 Feb 3.

Abstract

Problem: 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.

Method of study: 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.

Keywords: Anti-ovarian antibody; fertility; follicles; glucocorticoids; immunodominant epitopes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Cross Reactions
  • Dexamethasone / therapeutic use*
  • Disease Models, Animal
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • HSP90 Heat-Shock Proteins / immunology
  • Heat-Shock Proteins / immunology*
  • Humans
  • Immunodominant Epitopes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Ovary / drug effects*
  • Ovary / pathology
  • Primary Ovarian Insufficiency / diagnosis
  • Primary Ovarian Insufficiency / drug therapy*
  • Primary Ovarian Insufficiency / immunology
  • Recovery of Function / drug effects

Substances

  • Autoantibodies
  • Endoplasmic Reticulum Chaperone BiP
  • HSP90 Heat-Shock Proteins
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Hsp90b1 protein, mouse
  • Hspa5 protein, mouse
  • Immunodominant Epitopes
  • Dexamethasone