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Serum antibodies to EpCAM in healthy donors but not ulcerative colitis patients

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Abstract

Purpose: The gastrointestinal carcinoma-associated antigen epithelial cell adhesion molecule (EpCAM) has been a target for passive and active immunotherapy of gastrointestinal carcinoma patients. The antigen is expressed by both tumor and normal tissues. The immunogenicity of EpCAM in colorectal cancer patients has been described previously. The purpose of this study was to evaluate humoral and cellular immune responses of healthy individuals and ulcerative colitis patients to EpCAM and to relate immune responses to colonic tissue expression of EpCAM. Methods: An inhibition radioimmunoassay was used to detect anti-EpCAM serum antibodies. Anti-EpCAM antibodies of a healthy donor were expressed by phages and sequenced. 3H-thymidine incorporation assay was used for detection of lymphoproliferative responses to stimulation with EpCAM. EpCAM tissue expression was determined by immunohistochemistry. Results: We detected anti-EpCAM serum antibodies in 4 of 10, and EpCAM-specific lymphoproliferation responses in 1 of 10 healthy volunteers. The majority of anti-EpCAM antibodies derived from a healthy donor were germline-encoded. In contrast, none of the 23 patients with ulcerative colitis showed serum antibodies to EpCAM (P=0.005). Antigen expression was greatly reduced and altered in ulcerative colitis patients, whereas colon from healthy individuals and uninvolved colon of colorectal cancer patients expressed high levels of EpCAM. Conclusion: The results of these studies suggest an association between EpCAM antibody production and colonic EpCAM expression in healthy individuals and patients with ulcerative colitis. Decreased and altered colonic EpCAM expression in ulcerative colitis patients may be related to the disease induction, based on the previously demonstrated adhesion function of this molecule. Healthy individuals with anti-EpCAM immune responses and high risk for developing colorectal carcinoma are prime candidates for prophylactic immunization against EpCAM.

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Acknowledgements

We thank X. Li for expert technical assistance. This work was supported by grants CA74294 and CA10815 from the National Institutes of Health and the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA

    Emma E. Furth & Alyson C. Solomon

  2. The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA

    Jian Li, Enkhtsetseg Purev, Tianqian Zhang, Rajasekharan Somasundaram, Rolf Swoboda & Dorothee Herlyn

  3. Department of Internal Medicine I, University of Regensburg,  , Germany

    Gerhard Rogler

  4. Department of Biostatistics and Epidemiology, University of Pennsylvania, 19104, Philadelphia, PA, USA

    Rosemarie Mick & Mary Putt

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  1. Emma E. Furth
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Emma E. Furth and Jian Li contributed equally

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Furth, E.E., Li, J., Purev, E. et al. Serum antibodies to EpCAM in healthy donors but not ulcerative colitis patients. Cancer Immunol Immunother 55, 528–537 (2006). https://doi.org/10.1007/s00262-005-0026-5

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