TY  - JOUR
A1  - Wunsch, Marie
A1  - Zhang, Wenji
A1  - Hanson, Jodi
A1  - Caspell, Richard
A1  - Karulin, Alexey Y.
A1  - Recks, Mascha S.
A1  - Kuerten, Stefanie
A1  - Sundararaman, Srividya
A1  - Lehmann, Paul V.
T1  - Characterization of the HCMV-Specific CD4 T Cell Responses that Are Associated with Protective Immunity
JF  - Viruses
N2  - Most humans become infected with human cytomegalovirus (HCMV). Typically, the immune system controls the infection, but the virus persists and can reactivate in states of immunodeficiency. While substantial information is available on the contribution of CD8 T cells and antibodies to anti-HCMV immunity, studies of the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 subsets have been limited by the low frequency of HCMV-specific CD4 T cells in peripheral blood mononuclear cell (PBMC). Using the enzyme-linked Immunospot\(^{®}\) assay (ELISPOT) that excels in low frequency measurements, we have established these in a sizable cohort of healthy HCMV controllers. Cytokine recall responses were seen in all seropositive donors. Specifically, interferon (IFN)-\({\gamma}\) and/or interleukin (IL)-17 were seen in isolation or with IL-4 in all test subjects. IL-4 recall did not occur in isolation. While the ratios of T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 cells exhibited substantial variations between different individuals these ratios and the frequencies were relatively stable when tested in samples drawn up to five years apart. IFN-\({\gamma}\) and IL-2 co-expressing polyfunctional cells were seen in most subjects. Around half of the HCMV-specific CD4 cells were in a reversible state of exhaustion. The data provided here established the T\(_{H}\)1, T\(_{H}\)2, and T\(_{H}\)17 characteristic of the CD4 cells that convey immune protection for successful immune surveillance against which reactivity can be compared when the immune surveillance of HCMV fails.
KW  - memory cells
KW  - hcv infection
KW  - signature
KW  - Enzyme-Linked Immunospot assay (ELISPOT)
KW  - cytokine secretion kinetics
KW  - chronic viral infection
KW  - HCMV infection
KW  - CD4 T cells
KW  - exhaustion
KW  - activation
KW  - human cytomegalovirus (HCMV)
KW  - B cells
KW  - cytomegalovirus
KW  - elispot
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151462
VL  - 7
SP  - 4414
EP  - 4437
ER  - 
TY  - JOUR
A1  - Keller, Andreas
A1  - Leidinger, Petra
A1  - Vogel, Britta
A1  - Backes, Christina
A1  - ElSharawy, Abdou
A1  - Galata, Valentina
A1  - Mueller, Sabine C.
A1  - Marquart, Sabine
A1  - Schrauder, Michael G.
A1  - Strick, Reiner
A1  - Bauer, Andrea
A1  - Wischhusen, Jörg
A1  - Beier, Markus
A1  - Kohlhaas, Jochen
A1  - Katus, Hugo A.
A1  - Hoheisel, Jörg
A1  - Franke, Andre
A1  - Meder, Benjamin
A1  - Meese, Eckart
T1  - miRNAs can be generally associated with human pathologies as exemplified for miR-144*
JF  - BMC MEDICINE
N2  - Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists. 
Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR. 
Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 ( 95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait. 
Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
KW  - peripheral blood
KW  - microna profiles
KW  - disease
KW  - signature
KW  - expression
KW  - miRNA
KW  - microarray
KW  - biomarker
KW  - bioinformatics
KW  - lung-cancer
KW  - multiple sclerosis
KW  - gene
KW  - serum
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114349
SN  - 1741-7015
VL  - 12
ER  -