Prevalence, specificity and significance of ovarian antibodies during spontaneous premature ovarian failure

Autoimmunity may be involved in idiopathic premature ovarian failure (POF). However, the frequency, physiopathology and potential reversibility of autoimmune oophoritis needs clarification. Using an ELISA against whole tissue homogenate as antigen, from human ovaries at different ages, positive circulating ovarian antibodies (AOA) were found in 59% of patients with primitive idiopathic POF (27/46); 20/27 were positive for IgG isotype, 9/27 for IgM and 8/27 for IgA. Specificity of AOA was examined (i) by comparison to different control groups; mean values of the three subclasses of immunoglobins were significantly higher in POF women than in normally cycling fertile young women (n = 23) and fertile young men (n = 17), in untreated Grave's disease (n = 35) or in women with positive antinuclear factor (n = 25); and (ii) by assessing possible cross-reaction; only six out of the 27 positive sera reacted with other tissues (thyroid, pancreas, adrenal), including four clinical polyendocrinopathies. Significance of AOA was explored (i) by comparison with postmenopausal women (n = 40) and older women (n = 15), who did not have enhanced ratios of AOA, thereby excluding a potential role of high FSH values; (ii) by analysing the factors time and surgery; no relation could be found either with the duration of amenorrhoea (6 months to 21 years) or with the history of an ovarian biopsy (12/47) in the absence of any associated pelvic surgery; and (iii) by screening for other immunological factors; familial or personal autoimmune disease (8/46), HLA DR3 (10/42), HLA DR4 (11/42), associated autoantibodies (thyroperoxidase, adrenal, beta islets, parathyroid, DNA, smooth muscles) (12/42). If one positive AOA isotype was present, a second immunological factor was found in 45% of cases. Spontaneous pregnancies during oestrogen therapy occurred in four cases, including three women with positive AOA. Circulating AOA detected by an ELISA may represent a practical and suitable marker for diagnosis of POF. Its use for prognosis and rational treatment needs further evaluation.