Mechanisms and Models of Immune Tolerance Breakdown in the Ovary

ABSTRACT

Ovarian autoimmunity is increasingly implicated in the etiology of primary ovarian insufficiency (POI), previously termed premature ovarian failure or premature menopause. Links to autoimmunity in human POI have long been noted due to the close association of POI with several autoimmune diseases and syndromes such as Addison's disease and Autoimmune polyglandular syndrome 1. However, diagnosis of autoimmune-mediated POI (aPOI) remains challenging because of the lack of sensitive or specific markers of disease. Autoimmunity can arise from the breakdown of immunological tolerance in several ways. How then may we discern what constitutes a relevant target and what represents a downstream phenomenon? The answer lies in the study of pathogenic mechanisms in translational models of disease. From examples in humans and mice, we see that ovarian autoimmunity likely arises from a limited number of antigens targeted in the ovary that are organ specific. These antigens may be conserved but not limited to those seen in animal models of autoimmune ovarian disease. Recent advances in these areas have begun to define the relevant antigens and mechanisms of immune tolerance breakdown in the ovary. Work in translational models continues to provide insight into mechanisms of disease pathogenesis that will allow more accurate diagnosis and, ultimately, improved interventions for women with aPOI.

KEYWORDS

Primary ovarian insufficiency - ovarian autoimmunity - SCA-POI - APS1 - ovarian failure

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