Background/Purpose:

IL-17 and IL-22 are important cytokines in pathogenesis of spondyloarthropathy. In an IL-23 or IL-22 over-expressing mouse model it was shown that enthesitis is dependent on IL-22. IL-22 is mainly produced by T cells and innate cells. In enthesitis related arthritis (ERA) category of Juvenile arthritis enthesitis is an important clinical feature. As there is no data available on IL-22 in ERA we studied if IL-22 has any role to play in ERA and does it correlate with enthesitis by measuring the frequency of IL-22 producing T cells in blood and synovial fluid.

Methods:

Forty patients with JIA-ERA as per ILAR criteria for the diagnosis of JIA were included in the study. Heparinized blood (PB) sample was collected from all cases after consent. While synovial fluid (SF) was collected from only those patients who required therapeutic joint aspiration. The disease activity was assessed by Juvenile spondyloarthropathy disease activity score (JSpADA) and enthesitis score by MASES index. Childhood Health activity score (CHAQ) was done to assess disability. Seven healthy subjects and 8 polyarticular JIA patients were included as control. The disease activity was classified as high if JSpADA score was more than 2.5.

Th1, Th17 and Th22 cell frequency in blood and synovial fluid was measured after stimulating the cells with PMA and Ionomycin for 6 hours and adding secretion inhibitor Brefeldin A 10mg/ml to prevent secretion of cytokines. Later cells were surface stained with anti-human CD3/CD4 antibody for 30 minutes. The cells were fixed and permeabilised with cytofix/cytoperm kit for 20 minutes and then stained with intracellular cytokine PE labeled anti human PerCP-IL22 for 45 minutes. The sample was acquired using FACS Canto II and analyzed using flow Jo software. All analysis was done using non-parametric tests. All frequencies are referred as median(interquartile range).

Results:

There were 42 children with ERA of which 35 were male. The mean age for ERA, Polyarticular JIA and healthy controls was 15.45±2.83, 13.62±4.63 and 18 yrs respectively. Thirty-four patients (80%) had arthritis, 28 (66%) had enthesitis and 5 (12%) had uveitis. Mean JSpADA score was 3.85± 1.63.

The frequency of Th1, Th17 and Th22 cells in peripheral blood was similar between patients with ERA, Poly JIA and healthy controls.

In 10 paired samples (PB and SF) the median frequency of Th1 cells were higher in SF (9.3[4.3-19.1] as compared to peripheral blood (2.8 [2.2-3.42]; p<0.02) but the frequency of Th17 (0.4[0.2-1.1] Vs 0.2[ 0.2-0.325]) and Th22 (0.35[ 0.2-1.3] Vs 0.25 [0.2- 0.4]) though higher did not reach statistical significance.

The frequency of Th22 cells in PB was higher in children with high disease activity (0.2 [0.1-0.2]) as compared to children with minimally active/inactive disease (0.2[0.1-0.3] p<0.05). However, Th22 cell frequency had no correlation with disability as measured by CHAQ score or presence of enthesitis.

Conclusion: Th22 cells may contribute to inflammation in children with ERA however they do not have any association with enthesitis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/th22-cells-in-peripheral-blood-and-synovial-fluid-of-patients-with-enthesitis-related-arthritis/