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

ABSTRACT: INTRODUCTION: CD4+ T cells express K(2P)5.1 (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 K(2P)5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K(2P)5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. METHODS: Expression levels of K(2P)5.1 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 K(2P)5.1. RESULTS: K(2P)5.1 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, K(2P)5.1 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 K(2P)5.1 expression to disease activity parameters during a longitudinal follow-up for six months. CONCLUSIONS: Disease activity in RA patients correlates strongly with K(2P)5.1 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 K(2P)5.1 as a potential biomarker for disease activity and differential diagnosis.

SUBMITTER: Bittner S

PROVIDER: S-EPMC3241365 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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

Bittner Stefan S Bobak Nicole N Feuchtenberger Martin M Herrmann Alexander M AM Göbel Kerstin K Kinne Raimund W RW Hansen Anker J AJ Budde Thomas T Kleinschnitz Christoph C Frey Oliver O Tony Hans-Peter HP Wiendl Heinz H Meuth Sven G SG

Arthritis research & therapy 20110211 1

<h4>Introduction</h4>CD4+ T cells express K(2P)5.1 (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 K(2P)5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K(2P)5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients.<h4>Methods ...[more]

PMID: 21314928

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Project description:BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF 165). It has been shown that Sema3A competitively antagonizes VEGF 165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients. METHODS: Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney's inflammation scoring system. The localization of Sema3A, VEGF 165 and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels of Sema3A, VEGF-A and NRP1 mRNA were determined using quantitative real-time polymerase chain reaction (qPCR). RESULTS: In OA specimens, Sema3A, VEGF 165 and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction of Sema3A mRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio of Sema3A/VEGF-A mRNA expression levels with DAS28-CRP (R = -0.449, p = 0.013). Sema3A mRNA levels also correlated with Rooney's inflammation score, especially in perivascular infiltrates of lymphocytes (R = -0.506, p = 0.004), focal aggregates of lymphocytes (R = -0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = -0.536, p = 0.002). CONCLUSIONS: Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.

Project description:OBJECTIVE:To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). METHODS:This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. RESULTS:441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (? = -0.11, p<0.01), Simplified Disease Activity Index (SDAI) (? = -0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (? = -0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (? = -0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: "seafoods", "vegetables/fruits", "meats/fried foods", "snacks", and "processed foods". The multivariate analysis adjusted for clinically significant confounders showed that "seafoods" had statistically significant negative correlations with DAS28-ESR (? = -0.15, p<0.01), SDAI (? = -0.18, p<0.001), MMP-3 (? = -0.15, p<0.01), and HAQ (? = -0.24, p<0.0001). "Vegetables/fruits" had statistically significant negative correlations with SDAI (? = -0.11 p<0.05), MMP-3 (? = -0.12, p<0.01), and HAQ (? = -0.11, p<0.05). CONCLUSIONS:These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity.

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

Publications

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

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