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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-143711
  • 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 WeBackground 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.show moreshow less

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Metadaten
Author: Peter U. Ardelt, Jan Ebbing, Fabian Adams, Cora Reiss, Wadih Arap, Renata Pasqualini, Alexander Bachmann, Ulrich Wetterauer, Hubertus Riedmiller, Burkard Kneitz
URN:urn:nbn:de:bvb:20-opus-143711
Document Type:Journal article
Faculties:Medizinische Fakultät / Urologische Klinik und Poliklinik
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2015
Volume:10
Issue:3
Pagenumber:e0118646
Source:PLoS ONE 10(3): e0118646 (2015). DOI: 10.1371/journal.pone.0118646
DOI:https://doi.org/10.1371/journal.pone.0118646
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Bacillus-Calmette-Guerin; cancer surveillance; immune response; immunotherapy; protein biomarkers; system bcg; tumor cells; ubiquitin
Release Date:2018/06/01
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International