13933
2011
eng
R21
13
article
1
2016-10-14
--
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Expression of K\(_2\)\(_P\)5.1 potassium channels on CD4\(^+\)T lymphocytes correlates with disease activity in rheumatoid arthritis patients
Introduction
CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients.
Methods
Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1.
Results
K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K2P5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K2P5.1 expression to disease activity parameters during a longitudinal follow-up for six months.
Conclusions
Disease activity in RA patients correlates strongly with K2P5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K2P5.1 as a potential biomarker for disease activity and differential diagnosis.
Arthritis Research & Therapy
10.1186/ar3245
urn:nbn:de:bvb:20-opus-139334
Arthritis Research & Therapy 2011 13:R21.
Stefan Bittner
Nicole Bobak
Martin Feuchtenberger
Alexander M Herrmann
Kerstin Göbel
Raimund W Kinne
Anker J Hansen
Thomas Budde
Christoph Kleinschnitz
Oliver Frey
Hans-Peter Tony
Heinz Wiendl
Sven G Meuth
eng
uncontrolled
neurology
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13933/050_Bittner_Arthritis-Research-and-Therapy.pdf
15145
2015
eng
16880
16896
16
article
1
2017-07-13
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Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms
Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.
International Journal of Molecular Sciences
10.3390/ijms160816880
urn:nbn:de:bvb:20-opus-151454
International Journal of Molecular Sciences 2015, 16, 16880-16896. DOI: 10.3390/ijms160816880
026155
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Stefan Bittner
Nicole Bobak
Majella-Sophie Hofmann
Michael K. Schuhmann
Tobias Ruck
Kerstin Göbel
Wolfgang Brück
Heinz Wiendl
Sven G. Meuth
eng
uncontrolled
domain potassium channels
eng
uncontrolled
volume regulation
eng
uncontrolled
multiple-sclerosis
eng
uncontrolled
potassium channels
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
ion channels
eng
uncontrolled
K+ channel
eng
uncontrolled
T lymphocytes
eng
uncontrolled
up-regulation
eng
uncontrolled
TASK2
eng
uncontrolled
K2P channels
eng
uncontrolled
B cells
eng
uncontrolled
ph
eng
uncontrolled
K\(_{2P}\)5.1
eng
uncontrolled
KCNK5
eng
uncontrolled
autoimmune neuroinflammation
eng
uncontrolled
EAE
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15145/011_Bittner_International_Journal_of_Molecular_Science.pdf