Anti-HE4 antibodies in infertile women and women with ovarian cancer

- Anti-HE4 antibodies more common in infertility
- Correlate with antibodies to mesothelin

ObjectivesTo develop an assay for anti-HE4 antibodies and assess such antibodies in sera from women with increased epidemiologic risk for ovarian cancer (infertility) and patients with ovarian cancer in comparison to controls.MethodsAn ELISA was developed to measure antibodies to recombinant full length HE4 and cut-off values were determined for different levels of specificity (up to 99%).ResultsInfertile women more frequently had anti-HE4 antibodies than controls (23% at 98% specificity, p < 0.001) with antibodies most frequent in women with POF (31%) and ovulatory dysfunction (47%). There was also an increased frequency of anti-HE4 antibodies in patients with ovarian cancer (14% at 97% specificity, p < 0.01), but more women with certain types of infertility have anti-HE4 antibodies than women with ovarian cancer. Most patients with ovarian cancer have circulating HE4 antigen, which may interfere with detection of antibodies, while the level of HE4 antigen in sera from infertile women was not higher than in normal controls. There was a statistically significant correlation between antibodies to HE4 and antibodies to mesothelin in the same patients.ConclusionsWomen with certain types of infertility, which have increased risk to develop ovarian cancer, and women with ovarian cancer more frequently than controls have antibodies to HE4, a biomarker for ovarian cancer. The antibodies may reflect a tumor-promoting Th2 type of inflammation.