Autoimmunity and premature ovarian failure.
OBJECTIVE
The different patterns of autoreactivity that may account for the premature infertility observed in patients with premature ovarian failure are described.


RESULTS
Animal model studies have detailed fundamental immune dysregulatory patterns that induce ovarian failure in the context of global polyglandular involvement, as well as autoimmune mechanisms that induce ovarian failure in the context of targeted ovarian pathology. Recent studies on premature ovarian failure patients implicate the ubiquitously expressed glycolytic enzyme, alpha-enolase, as a potential antigenic target, particularly in those patients with polyglandular involvement; and the ovarian-specific maternal-effect protein, Mater, whose expression is essential for fertility.


CONCLUSIONS
Several fundamentally distinct mechanisms may account for premature ovarian failure, including global immune dysregulation, particularly in patients with polyglandular autoimmunity. Premature ovarian failure may also be due to inflammatory autoimmunity targeted to ovarian-specific germline antigens (e.g., zona pellucida proteins or Mater) or differentiation/regulatory factors (e.g., inhibin-alpha). Moreover, the ovarian autoimmunity may be mediated by T cells (e.g., those targeting zona pellucida proteins) or B cells/antibodies (e.g., those targeting inhibin-alpha). Thus premature ovarian failure appears to be a complex disease entity with multiple underlying etiopathogenic contributions including the possibility of several distinctly different autoimmune mechanisms.
Tuohy
Vincent K
VK
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Ohio 44195, USA. tuohyv@ccf.org
Altuntas
Cengiz Z
CZ
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000209:etiology* / Q000276:immunology*
D001323:Autoantibodies