TY  - JOUR
A1  - Ardelt, Peter U.
A1  - Ebbing, Jan
A1  - Adams, Fabian
A1  - Reiss, Cora
A1  - Arap, Wadih
A1  - Pasqualini, Renata
A1  - Bachmann, Alexander
A1  - Wetterauer, Ulrich
A1  - Riedmiller, Hubertus
A1  - Kneitz, Burkard
T1  - An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder
JF  - PLoS ONE
N2  - 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.
KW  - Bacillus-Calmette-Guerin
KW  - immune response
KW  - ubiquitin
KW  - protein biomarkers
KW  - system bcg
KW  - tumor cells
KW  - immunotherapy
KW  - cancer surveillance
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143711
VL  - 10
IS  - 3
ER  -