Expression of Interleukin-17 in Synovial Fluid & Peripheral Blood in Juvenile Idiopathic Arthritis

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Presentation Number:F58

Poster Board Number:596

Presentation Time:11/9/2007 8:00:00 AM

Title:Expression of Interleukin-17 in Synovial Fluid and Peripheral Blood in

Juvenile Idiopathic Arthritis

Category:12. Pediatric rheumatology pathogenesis and genetics

Author(s):Roman Jurencak1, Trang T. Duong2, Lyndon J. Chung2, M.

Feldman1, Rae S.M. Yeung2. 1Division of Rheumatology, Hospital for Sick

Children, Toronto, ON, Canada; 2Cell Biology Research Program, Hospital for

Sick Children, Toronto, ON, Canada

Background: Interleukin-17 (IL-17) is a proinflammatory cytokine which

contributes to joint inflammation and destruction. High levels of IL-17 have

been detected in the synovial fluid (SF) of patients with rheumatoid

arthritis (RA) and overexpression studies suggest that IL-17 enhances the

inflammatory and destructive capacity of IL-1 and tumor necrosis factor α

(TNF), with strong synergistic effect on chondrocyte death. Ex vivo models

showed that the combination of TNF blockade with IL-17 blockade is more

effective for controlling synovial inflammation and bone resorption

suggesting new therapeutic possibilities in RA. However, the role of IL-17

in juvenile idiopathic arthritis (JIA) is currently not clear.

Objectives: To examine the relation of IL-17 expression in SF or peripheral

blood lymphocytes (PBL) and disease activity in children with JIA.

Methods: 38 SF and 24 PBL samples, collected at time of intra-articular

joint injections, were available for analysis. The specimens were

centrifuged over a Ficoll gradient and mononuclear cells were isolated and

immediately suspended in TRIzol reagent. Total RNA was isolated and cDNA

synthesized using murine leukemia virus reverse transcriptase and the

GeneAmp RNA PCR kit (Applied Biosystems). IL-17 cDNA was then amplified by

real-time PCR (Applied Biosystems). Quantitative RT-PCR was used to

determine relative mRNA levels of IL-17. GAPDH (house-keeping gene) was

amplified for each sample to control for sample-to-sample variability and

differences in reverse transcriptase efficiency. Relationship of IL-17 and

disease activity (active joint count) was analyzed using general linear

modeling.

Results: Patients’ characteristics are summarized in Table 1. We found

significant association between expression of IL-17 in PBL (but not in SF)

and disease activity. However, this relationship was strongly influenced by

a very high IL-17 expression in a patient with the greatest number of active

joints. The relationship of disease activity and IL-17 expression in PBL or

SF was not significantly different among the subtypes of JIA.

Conclusion: Results of this study suggest a relationship between JIA

activity and IL-17 expression in PBL. However, our study was limited by the

small number of patients and relatively low disease activity in the entire

group. We hypothesize that IL-17 production by circulating lymphocytes might

play a far more important role in polyarticular disease than in other JIA

subtypes. Larger studies are needed to confirm this hypothesis.

Disclosures: R. Jurencak, None; T.T. Duong, None; L.J. Chung, None; B.M.

Feldman, None; R.S. Yeung, None.