An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder.
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.
Department of Urology, University Hospital Basel, Basel, Switzerland; Department of Urology and Pediatric Urology, Medical School, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; Department of Urology, Bavarian Julius Maximilians-University Medical School, Würzburg, Germany.
Peter U
PU
Ardelt
Department of Urology, University Hospital Basel, Basel, Switzerland.
Jan
J
Ebbing
Department of Urology and Pediatric Urology, Medical School, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Fabian
F
Adams
Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center Mainz, Mainz, Germany.
Cora
C
Reiss
Division of Hematology/Oncology and Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Wadih
W
Arap
Division of Hematology/Oncology and Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Renata
R
Pasqualini
Department of Urology, University Hospital Basel, Basel, Switzerland.
Alexander
A
Bachmann
Department of Urology and Pediatric Urology, Medical School, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Ulrich
U
Wetterauer
Department of Urology, Bavarian Julius Maximilians-University Medical School, Würzburg, Germany.
Hubertus
H
Riedmiller
Department of Urology, Bavarian Julius Maximilians-University Medical School, Würzburg, Germany.
Burkhard
B
Kneitz
D000917:Antibody Formation; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000473:pathology; D018604:Epitope Mapping; D006801:Humans; D025801:Ubiquitin / Q000276:immunology*; D001743:Urinary Bladder / Q000276:immunology* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology
D025801:Ubiquitin