A block in the road to fertility: autoantibodies to heat-shock protein 90-beta in human ovarian autoimmunity.
OBJECTIVE
To report autoantibodies to human heat-shock protein 90-beta (HSP90 beta) in sera of women with infertility.


METHODS
Prospective, controlled observations.


METHODS
Major urban infertility referral center and research institution.


METHODS
Fifty women with premature ovarian failure, 65 infertile women enrolled in the in vitro fertilization-embryo transfer program, and 60 normally menstruating fertile women as controls.


METHODS
None.


METHODS
Identification and complete characterization of a 90-kd protein, the most immunodominant autoantigen.


RESULTS
Our previous studies employing a novel blocking demonstrated several cellular and molecular ovarian antigenic targets using patient's serum. Of all these antigens, the 90-kd protein designated as EP90 was found to be conserved across species, was serine-threonine phosphorylated, and was expressed from the primordial stage to the graafian-stage ooplasm of the oocytes during follicular development. Using high-throughput proteomic technologies like liquid chromatography/mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF), and tandem mass spectrometry analysis revealed the identity of this protein to be HSP90 beta. Commercially available recombinant protein immunoreacted with the sera from patients with antiovarian antibodies against the 90-kd antigen. In parallel, using monoclonal antibody to human HSP90, we found that it reacts with the eluted protein from a crude ovarian extract.


CONCLUSIONS
This is the first report to show the presence of ovarian autoantibodies to human HSP90 in sera of women with infertility. This protein could be involved in human ovarian autoimmunity and thereby be a causative factor in early ovarian failure.
Pires
Eusebio S
ES
Department of Gamete Immuno Biology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai, India.
Khole
Vrinda V
VV
Department of Gamete Immuno Biology, National Institute for Research in Reproductive Health (Indian Council of Medical Research), Parel, Mumbai, India. Electronic address: kholevv@icmr.org.in.
D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005298:Fertility / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology* / Q000276:immunology; D051379:Mice; D010053:Ovary / Q000276:immunology / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000150:complications / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
D001323:Autoantibodies; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human