Autoantibodies to Mesothelin in Infertility

Luborsky, Judith L.; Yu, Yinhua; Edassery, Seby L.; Jaffar, Jade; Yip, Yuan Yee; Liu, Pu; Hellström, Kjell; Hellström, Ingegerd

doi:10.1158/1055-9965.epi-11-0139

Cited by 12 publications

(11 citation statements)

References 83 publications

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“…The finding in this study is similar to our previous study of anti-mesothelin (Luborsky et al 2011). Overall the results suggest that anti-SBP1 in women with infertility related to ovarian insufficiency may be a measurable indicator of risk for ovarian cancer.…”

Section: Discussionsupporting

confidence: 93%

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Selenium-Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer

Yu-Rice¹,

Edassery²,

Urban³

et al. 2017

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Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to Selenium Binding Protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n=41), infertility (n=92) and control (n=87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1 positive sera was higher in POF (p=0.02), irregular ovulation (p=0.001), unexplained causes (p=0.02), late (III–IV) stage OvCa (p=0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I–II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (p=0.04) but not non-serous (p=0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-p53, markers often studied in OvCa. Anti-p53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls, or when combined with anti-p53 and CA125, to identify OvCa was evaluated by comparing the Area Under the Curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC=0.7; p=0.001) or OvCa (AUC=0.67; p=0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-p53 and anti-SBP1 (AUC=0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with development of serous OvCa.

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Section: Discussionsupporting

confidence: 93%

“…In summary, this is the first study to demonstrate SBP1 autoantibodies in ovarian insufficiency and cancer and is an extension of our previous reports of anti-mesothelin (Luborsky et al 2011) and anti-HE4 (Hellstrom et al 2013) in ovarian cancer. Thus there appears to be a link between autoantibodies in infertility and serous ovarian cancer.…”

Section: Discussionsupporting

confidence: 79%

Selenium-Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer

Yu-Rice¹,

Edassery²,

Urban³

et al. 2017

Reproduction

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“…The samples tested for antibodies to HE4 had previously been tested for antibodies to mesothelin [24]. We next investigated whether women forming antibodies to one antigen (mesothelin or HE4) were more likely to also have antibodies to the other antigen.…”

Section: Resultsmentioning

confidence: 99%

“…Antibodies to mesothelin have been detected in women with OvC [21, 22] and in sera from women with pelvic inflammatory disease [22], a condition associated with an increased frequency of OvC [23]. Likewise, women with certain types of infertility have antibodies to mesothelin more frequently than controls [24]. HE4, human epididymis factor 4 [25], which is expressed by OvC, particularly its serous type [26, 27], and in lung adenocarcinoma [28] is attracting attention as a diagnostic marker which can complement CA125 since it is less often elevated in benign conditions and can be applied in combination with CA125 to aid diagnosis of women with a pelvic mass [20, 29-31].…”

Section: Introductionmentioning

confidence: 99%

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

Hellström

Swisher

Hellström

et al. 2013

Gynecologic Oncology

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Objectives To 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. Methods An 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%). Results Infertile 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. Conclusions Women 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.

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“…Both women with infertility and those with ovarian cancer have autoantibodies to ovarian antigens. Luborsky et al, 2011 showed for the first time that antibodies to mesothelin, a well-characterized ovarian cancer antigen, occur in some of the women with epidemiologic risk for ovarian cancer.…”

Section: Anti-ovarian Antibodies and Infertilitymentioning

confidence: 99%