Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis.

OBJECTIVE

A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.

METHODS

The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ss (IL-1ss), IL-6, IL-21, IL-23, and transforming growth factor ss (TGF-ss), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.

RESULTS

There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-gamma+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ss (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ss were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.

CONCLUSION

In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ss and IL-6 in SF may be responsible for increased Th17 cells.