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

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.