Autoantibodies to mesothelin in infertility

Abstract

Background: According to extensive epidemiologic 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 (POF; n = 25) and unexplained infertility (n = 44). Sera were assayed for mesothelin antibodies and for circulating mesothelin antigen by immunoassay and compared with 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 (44%) and unexplained infertility (25%) compared with 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 impact: 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.

Figure 1

Box plots of mesothelin antibody shown as optical density (OD) values by study group. Sera were tested at 1:20 (upper graph) and 1:100 (lower graph). Each box plot shows the median (50^th percentile; dark bar), values to the 1.5 interquartile range (whiskers), 25^th–75^th percentile range (box) and outliers (○, ★). The horizontal dotted line shows the cutoff value (mean serum control OD + 2SD) used to determine antibody positive results as summarized in Table 2.

Figure 2

Box plot of circulating mesothelin antigen levels (ng/mL) by study group. The box plot is described in Figure 1. The horizontal dotted line shows the mean normal value + 2SD for reference. Mean values for each group are summarized in Table 2.

Figure 3

Comparison of mesothelin antibody and circulating antigen in ovarian cancer (●) and benign tumor (△) groups. Mesothelin and anti-mesothelin were correlated in ovarian cancer (correlation coefficient corrected for age = 0.49, p=0.02). However, not all individuals with elevated mesothelin had anti-mesothelin antibodies.