Autoantigens in ovarian autoimmunity associated with unexplained infertility and premature ovarian failure.

OBJECTIVE: To identify ovarian autoantigens associated with ovarian autoantibodies. DESIGN: Hypothesis-generating prospective study. SETTING: Urban infertility referral centers and academic research institution. PATIENT(S): Seventy-four patients with infertility, 19 patients with premature ovarian failure (POF), and 16 healthy control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of autoantigens. RESULT(S): To identify major antigens for ovarian autoimmunity, sera from 74 women with unexplained infertility were screened for ovarian autoantibodies (AOAs) by immunoassay and one-dimensional Western blot. The majority of sera had immunoreactions at 50-56 kDa. Six representative positive infertility sera were used to identify antigens between 40 and 60 kD by two-dimensional Western blot and mass spectrometry. Antigens included aldehyde (retinal) dehydrogenases (ALDH1A1, ALDH1A2, and ALDH7A1), protein disulfide isomerase A3, vimentin, α-enolase, phosphoglycerate dehydrogenase, and selenium-binding protein 1 (SBP1). Sixty percent (24 out of 40) of infertility and POF sera were positive for recombinant ALDH1A1, SBP1, or enolase; 80.7% (21 out of 26) of AOA-positive sera had antibodies to one or more of the three antigens, and only 7% (1 out of 14) of AOA-negative sera had antibodies to recombinant proteins. CONCLUSION(S): ALDH1A1 and SBP1 are unique to ovarian autoimmunity associated with infertility and POF, and may provide the basis for specific tests to identify patients with ovarian autoimmunity.

Association of unexplained infertility with gonadotropin and ovarian antibodies.

PROBLEM: To determine the prevalence and characteristics of gonadotropin autoantibodies (GAB) associated with unexplained infertility, and to assess the relationship between ovarian autoantibodies (OVAB) and GAB. METHOD OF STUDY: Ovarian antibodies and GABs in sera of patients with unexplained infertility (n = 53) and a comparison (population) group from a blood bank (n = 40) were detected by immunoassay. Patients with unexplained infertility had either no prior gonadotropin treatment (n = 15) or two or more gonadotropin cycles to induce ovulation (n = 38). RESULTS: The GABs were detected in 67% of women with treatment, 27% of women without treatment and 8% of women in the population. The GABs recognized follicle stimulating hormone (FSH) and luteinizing hormone (LH) and their alpha and beta subunits and to a lesser extent thyroid stimulating hormone (TSH) and prolactin. There was no significant difference in OVAB prevalence between gonadotropin treated or untreated women while GABs were significantly more frequent in gonadotropin treated women (P < or = 0.01). CONCLUSION: Gonadotropin antibodies may represent a separate marker of ovarian autoimmunity in unexplained infertility as they are correlated with OVAB and are present in patients not treated with gonadotropin. However, as a higher frequency of GAB is associated with gonadotropin treatment, patients with ovarian autoimmunity may tend to have an immune response to gonadotropins in addition to an endocrine response.

Anti-tumor antibodies in ovarian cancer.

Anti-tumor antibodies have potential as cancer biomarkers. There is relatively limited identification of anti-tumor antibodies in response to ovarian cancer, compared with studies for other cancers. There is also very limited information on the prevalence of anti-tumor antibodies among ovarian cancer patients. Although most anti-tumor antibodies react with antigens common to both tumor and normal tissue, the anti-tumor response tends to be confined to individuals with ovarian cancer, similar to other cancers. Antibodies to HOXA7, a differentiation antigen, have the highest reported prevalence in ovarian cancer (67%). Antibodies to other ubiquitous antigens including NY-ESO-1, Ep-CAM (epithelial cell adhesion molecule), HSP-90 (heat shock protein 90), and mutated p53 have been identified in ovarian cancer. Anti-tumor antibody specificity reflects the heterogeneity of antigen expression in tumors. Tests based on panels of a combination of anti-tumor antibodies may be more predictive for ovarian cancer, as no single specificity accounts for ovarian tumors. In addition to characterization of anti-tumor antibodies as diagnostic markers, study of anti-tumor antibodies is likely to provide insights into mechanisms of tumor development. There is evidence of antibodies to tumor antigens and of activated T cells, suggesting immune recognition of tumor antigens occurred. Nonetheless, as tumors are not 'rejected', it is likely that there are alterations in the immune system. The basis for tumor growth in the face of immune activity remains to be determined.