AUTOANTIBODIES TO MESOTHELIN IN INFERTILITYa,,b,,c

Background—According to extensive epidemiological data, infertility is associated with increased ovarian cancer risk. Previous studies showed that both women with infertility and those with ovarian cancer have autoantibodies to ovarian antigens. The objective was to determine if women with infertility have antibodies to mesothelin, a well characterized ovarian cancer antigen. Methods—Sera were obtained from women with infertility (n=109), ovarian cancer (n=28), benign ovarian tumors or cysts (n=24) and from healthy women (n=152). Infertility included those with a risk for ovarian cancer; endometriosis (n=23), ovulatory dysfunction (n=17), premature ovarian failure (n=25) and unexplained infertility (n=44). Sera were assayed for mesothelin antibodies and for circulating mesothelin antigen by immunoassay and compared to assay control sera (n=16) to determine a positive result. Results—Mesothelin antibodies were significantly more frequent in women with prematurely reduced ovarian function including ovulatory dysfunction (59%), ovarian failure (POF) (44%) and unexplained infertility (25%) compared to controls. In contrast, women with endometriosis, who also have a high risk for ovarian cancer, did not have mesothelin antibodies. Serum levels of mesothelin were rarely elevated in women with infertility but were high in most patients with ovarian cancer. Conclusions and Significance—We show for the first time that antibodies to mesothelin, a well characterized ovarian cancer antigen, occur in some women with epidemiologic risk for ovarian cancer. The results suggest it may be possible to identify which women with infertility have ovarian cancer risk.