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  - 
TY  - JOUR
A1  - Aue, Annemarie
A1  - Englert, Nils
A1  - Harrer, Leon
A1  - Schwiering, Fabian
A1  - Gaab, Annika
A1  - König, Peter
A1  - Adams, Ralf
A1  - Schmidtko, Achim
A1  - Friebe, Andreas
A1  - Groneberg, Dieter
T1  - NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis
JF  - Respiratory Research
N2  - Background
The origin of αSMA-positive myofibroblasts, key players within organ fibrosis, is still not fully elucidated. Pericytes have been discussed as myofibroblast progenitors in several organs including the lung.

Methods
Using tamoxifen-inducible PDGFRβ-tdTomato mice (PDGFRβ-CreERT2; R26tdTomato) lineage of lung pericytes was traced. To induce lung fibrosis, a single orotracheal dose of bleomycin was given. Lung tissue was investigated by immunofluorescence analyses, hydroxyproline collagen assay and RT-qPCR.

Results
Lineage tracing combined with immunofluorescence for nitric oxide-sensitive guanylyl cyclase (NO-GC) as marker for PDGFRβ-positive pericytes allows differentiating two types of αSMA-expressing myofibroblasts in murine pulmonary fibrosis: (1) interstitial myofibroblasts that localize in the alveolar wall, derive from PDGFRβ+ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRβ de novo after injury), are negative for NO-GC, have a large multipolar shape and appear to spread over several alveoli within the injured areas. Moreover, NO-GC expression is reduced during fibrosis, i.e., after pericyte-to-myofibroblast transition.

Conclusion
In summary, αSMA/PDGFRβ-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.
KW  - guanylyl cyclase
KW  - myofibroblasts
KW  - pericytes
KW  - transgenic mouse
KW  - fibrosis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357805
VL  - 24
ER  -