This research proposal will characterize dominant ovarian antigens recognized by serum antibodies from patients with premature ovarian failure (POF) with the goals of better understanding the pathophysiology of POF and identifying biomarkers for diagnosis of autoimmune ovarian disease. Sera from patients with POF will be screened for antiovarian antibodies and then employed on 2-D gel immunoblots to identify immunoreactive proteins present in human and mouse ovarian and egg extracts. Immunoreactive ovarian and egg proteins will be microsequenced to identify candidate genes encoding ovarian and egg antigens. Peptide microsequences obtained by mass spectrometry will be compared to gene and protein databases to identify autoantigens. Full length cDNAs corresponding to ovarian/egg autoantigens will be cloned and recombinant antigens expressed in bacterial and yeast expression systems. The incidence of antibodies to one or more defined recombinant egg target antigens will then be determined in patients with POF and antiovarian antibodies. The studies are anticipated to lead to a deeper understanding of ovarian autoimmunity in humans and to improved methods of detecting antiovarian antibodies including the possibility of detecting early stage disease. Availability of better diagnostics for ovarian disease may also help in proper clinical follow up and selection of patients who may benefit from immunotherapy or assisted reproductive technologies (in vitro fertilization/embryo transfer [IVF/ET]) to recover their fertility. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD055129-02
Application #
7420897
Study Section
Special Emphasis Panel (ZHD1-DRG-D (JH))
Program Officer
Parrott, Estella C
Project Start
2007-05-07
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2008
Total Cost
$74,235
Indirect Cost
Name
University of Virginia
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904