Ann Lab Med.  2013 Jan;33(1):52-59. 10.3343/alm.2013.33.1.52.

Elevated Levels of T Helper 17 Cells Are Associated with Disease Activity in Patients with Rheumatoid Arthritis

• Kim J
• Kang S
• Kim J
• Kwon G
• Koo S

• KMID: 1781298
• DOI: http://doi.org/10.3343/alm.2013.33.1.52

Abstract

BACKGROUND
Interleukin-17 (IL-17)-producing T helper (Th) 17 cells are considered as a new subset of cells critical to the development of rheumatoid arthritis (RA). We aimed to investigate the distribution of Th1 and Th17 cells and their association with disease activity, and determine the Th17-related cytokine levels in the peripheral blood of RA patients.
METHODS
Peripheral blood mononuclear cells from 55 RA and 20 osteoarthritis (OA) patients were stimulated with mitogen, and the distributions of CD4+Interferon (INF)+IL-17- (Th1 cells) and CD4+INF-IL-17+ (Th17 cells) were examined by flow cytometry. Serum levels of IL-6, IL-17, IL-21, IL-23, and tumor necrosis factor (TNF)-alpha were measured by ELISA. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were recorded. The 28-joint disease activity score (DAS28) was also assessed.
RESULTS
The median percentage of Th17 cells was higher in RA patients than in OA patients (P=0.04), and in active than in inactive RA (P=0.03), whereas that of Th1 cells was similar in both groups. Similarly, the levels of IL-17, IL-21, and IL-23 were detected in a significantly higher proportion of RA patients than OA patients and the frequencies of detectable IL-6, IL-17, and IL-21 were higher in active RA than in inactive RA group. The percentage of Th17 cells positively correlated with the DAS28, ESR, and CRP levels.
CONCLUSIONS
These observations suggest that Th17 cells and Th17-related cytokines play an important role in RA pathogenesis and that the level of Th17 cells in peripheral blood is associated with disease activity in RA.

Keyword

Rheumatoid arthritis; T helper 1 cell; T helper 17 cell; Cytokines

MeSH Terms

Adult
Aged
Arthritis, Rheumatoid/blood/metabolism/*pathology
Blood Sedimentation
C-Reactive Protein/analysis
Cytokines/blood
Female
Humans
Male
Middle Aged
Osteoarthritis/blood/metabolism/pathology
Severity of Illness Index
Th1 Cells/cytology/immunology/metabolism
Th17 Cells/*cytology/immunology/metabolism
Cytokines
C-Reactive Protein

Figure

• 

  Fig. 1 The percentage of Th1 cells and Th17 cells in representative rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Lymphocytes (a) were gated in a forward scatter (FS)/side scatter (SS) dot plot, and then CD4+ T cells (b) within indicated lymphocytes were isolated. CD4+ T cells were divided into CD4+INFγ+IL17- (Th1 cells), CD4+INFγ-IL17+ (Th17 cells) and CD4+INFγ+IL17+ cells.Abbreviations: Th1, T helper 1; Th17, T helper 17; RA, rheumatoid arthritis; OA, osteoarthritis; INF, interferon; IL, interleukin.

• 

  Fig. 2 Frequencies of Th1 cells (A) and Th17 cells (B) in patients with active rheumatoid arthritis (RA), patients with inactive RA, and patients with osteoarthritis (OA). Horizontal lines represent median and error bars represent a 95% interval.Abbreviation: Th, T helper.

• 

  Fig. 3 Correlation between the percentage of Th17 cells and C-reactive protein (A) as well as DAS28 (B) in RA patients.Abbreviations: Th, T helper; DAS28, 28-joint disease activity score; RA, rheumatoid arthritis.

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