Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2011

Open Access 01-02-2011 | Research article

Expression of K2P5.1 potassium channels on CD4+T lymphocytes correlates with disease activity in rheumatoid arthritis patients

Authors: 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

Published in: Arthritis Research & Therapy | Issue 1/2011

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference van Vollenhoven RF: Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009, 5: 531-541. 10.1038/nrrheum.2009.182.CrossRef van Vollenhoven RF: Treatment of rheumatoid arthritis: state of the art 2009. Nat Rev Rheumatol. 2009, 5: 531-541. 10.1038/nrrheum.2009.182.CrossRef
2.
go back to reference Feuchtenberger M, Kneitz C, Roll P, Kleinert S, Tony HP: Sustained remission after combination therapy with rituximab and etanercept in two patients with rheumatoid arthritis after tnf failure: case report. Open Rheumatol J. 2009, 3: 9-13. 10.2174/1874312900903010009.CrossRef Feuchtenberger M, Kneitz C, Roll P, Kleinert S, Tony HP: Sustained remission after combination therapy with rituximab and etanercept in two patients with rheumatoid arthritis after tnf failure: case report. Open Rheumatol J. 2009, 3: 9-13. 10.2174/1874312900903010009.CrossRef
3.
go back to reference van Gestel AM, Haagsma CJ, van Riel PL: Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998, 41: 1845-1850. 10.1002/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K.CrossRef van Gestel AM, Haagsma CJ, van Riel PL: Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998, 41: 1845-1850. 10.1002/1529-0131(199810)41:10<1845::AID-ART17>3.0.CO;2-K.CrossRef
4.
go back to reference Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, Aletaha D, van Riel PL: Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009, 68: 954-960. 10.1136/ard.2007.084459.CrossRef Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, Aletaha D, van Riel PL: Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis. 2009, 68: 954-960. 10.1136/ard.2007.084459.CrossRef
5.
go back to reference Bittner S, Meuth SG, Gobel K, Melzer N, Herrmann AM, Simon OJ, Weishaupt A, Budde T, Bayliss DA, Bendszus M, Wiendl H: TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of the central nervous system. Brain. 2009, 132: 2501-2516. 10.1093/brain/awp163.CrossRef Bittner S, Meuth SG, Gobel K, Melzer N, Herrmann AM, Simon OJ, Weishaupt A, Budde T, Bayliss DA, Bendszus M, Wiendl H: TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of the central nervous system. Brain. 2009, 132: 2501-2516. 10.1093/brain/awp163.CrossRef
6.
go back to reference Meuth SG, Bittner S, Meuth P, Simon OJ, Budde T, Wiendl H: TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. J Biol Chem. 2008, 283: 14559-14570. 10.1074/jbc.M800637200.CrossRef Meuth SG, Bittner S, Meuth P, Simon OJ, Budde T, Wiendl H: TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions. J Biol Chem. 2008, 283: 14559-14570. 10.1074/jbc.M800637200.CrossRef
7.
go back to reference Bittner S, Bobak N, Herrmann AM, Göbel K, Meuth P, Höhn KG, Stenner MP, Budde T, Wiendl H, Meuth SG: Upregulation of K2P5.1 potassium channels in multiple sclerosis. Annals of Neurology. 2010, 68: 58-69. 10.1002/ana.22010.CrossRef Bittner S, Bobak N, Herrmann AM, Göbel K, Meuth P, Höhn KG, Stenner MP, Budde T, Wiendl H, Meuth SG: Upregulation of K2P5.1 potassium channels in multiple sclerosis. Annals of Neurology. 2010, 68: 58-69. 10.1002/ana.22010.CrossRef
8.
go back to reference Goronzy JJ, Weyand CM: Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther. 2009, 11: 249.CrossRef Goronzy JJ, Weyand CM: Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther. 2009, 11: 249.CrossRef
9.
go back to reference Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009, CD007277-4 Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009, CD007277-4
10.
go back to reference Dixon W, Massey F: Introduction to Statistical Analysis. 1969, New York: McGraw-Hill Companies Dixon W, Massey F: Introduction to Statistical Analysis. 1969, New York: McGraw-Hill Companies
11.
go back to reference Mima T, Nishimoto N: Clinical value of blocking IL-6 receptor. Curr Opin Rheumatol. 2009, 21: 224-230. 10.1097/BOR.0b013e3283295fec.CrossRef Mima T, Nishimoto N: Clinical value of blocking IL-6 receptor. Curr Opin Rheumatol. 2009, 21: 224-230. 10.1097/BOR.0b013e3283295fec.CrossRef
12.
go back to reference Funahashi K, Koyano S, Miura T, Hagiwara T, Okuda K, Matsubara T: Efficacy of tocilizumab and evaluation of clinical remission as determined by CDAI and MMP-3 level. Mod Rheumatol. 2009, 19: 507-512. 10.1007/s10165-009-0203-z.CrossRef Funahashi K, Koyano S, Miura T, Hagiwara T, Okuda K, Matsubara T: Efficacy of tocilizumab and evaluation of clinical remission as determined by CDAI and MMP-3 level. Mod Rheumatol. 2009, 19: 507-512. 10.1007/s10165-009-0203-z.CrossRef
13.
go back to reference Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC: Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010, 69: 88-96. 10.1136/ard.2008.105197.CrossRef Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC: Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010, 69: 88-96. 10.1136/ard.2008.105197.CrossRef
14.
go back to reference Matsui T, Komiya A, Shimada K, Nakayama H, Tohma S: Neutrophil CD64 as a marker of infection in patients treated with tocilizumab. Mod Rheumatol. 2009, 19: 696-697. 10.1007/s10165-009-0223-8.CrossRef Matsui T, Komiya A, Shimada K, Nakayama H, Tohma S: Neutrophil CD64 as a marker of infection in patients treated with tocilizumab. Mod Rheumatol. 2009, 19: 696-697. 10.1007/s10165-009-0223-8.CrossRef
Metadata
Title
Expression of K2P5.1 potassium channels on CD4+T lymphocytes correlates with disease activity in rheumatoid arthritis patients
Authors
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
Publication date
01-02-2011
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2011
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3245

Other articles of this Issue 1/2011

Arthritis Research & Therapy 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.