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.

Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction.

Immunoproteomics using sera of women with ovarian autoimmune diseases such as primary ovarian insufficiency and IVF embryo transfer recruits led to identification of three proteins namely alpha actinin 4 (α-ACTN4), heat-shock 70 protein 5 (HSPA5), and actin beta (ACTB). This study deals with the establishment of a peptide ELISA for screening sera of antiovarian antibody (AOA)-positive patients and further delves into understanding the role of these three proteins in ovarian autoimmunity in a mouse model. Using in silico approach, antigenic peptides of these proteins were identified and used for peptide ELISA.

Identification and validation of candidate biomarkers involved in human ovarian autoimmunity.

Antibodies to multiple ovarian antigens have been proposed as markers of ovarian autoimmunity. The role of ovarian autoantibodies has been widely discussed in the pathophysiology of premature ovarian failure and unexplained infertility, but the autoantigens are yet to be identified. Three immunodominant ovarian autoantigens, α-actinin 4 (αACTN4), heat shock 70 protein 5 (HSPA5) and β-actin (ACTB), have been identified using anti-ovarian antibody-positive sera from women with idiopathic premature ovarian failure (n=50) and women undergoing IVF (n=695), using mass spectrometry.

Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

Objective: To establish importance of anti-ovarian antibodies (AOA) testing in infertile women.

Design: A clinical reproductive outcome comparative study between two groups of women undergoing IVF-ET. Group 1 consists of women tested positive for AOA, put on corticosteroid therapy, reverted to AOA negative and then taken up for IVF-ET.