An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder

PLoS One. 2015 Mar 5;10(3):e0118646. doi: 10.1371/journal.pone.0118646. eCollection 2015.

Abstract

Background: To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder.

Methods: A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin.

Results: We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy.

Conclusions: This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation*
  • Carcinoma, Transitional Cell / immunology*
  • Carcinoma, Transitional Cell / pathology
  • Epitope Mapping
  • Humans
  • Ubiquitin / immunology*
  • Urinary Bladder / immunology*
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Ubiquitin

Grant support

This work was partly funded by a non restricted fund from medac, Wedel, Germany. The funders had no role in study design, data collection and Analysis, decision to publish or preparation of the manuscript. The other funding was internal from our institution.