Enthesitis-related arthritis (ERA) is a category of juvenile idiopathic arthritis. Different proinflammatory cytokines linked to the Th1 and Th17 T- cell subsets have been implicated in its pathogenesis. Limited data are currently available about the relationship between disease activity and the clinical pattern and the percentage of Th1/ Th17 T- cell subsets. Our objectives were  to analyze Th1 and Th17 cell subsets in patients with ERA and to compare with age-matched healthy controls. To assess the association between disease activity and disease clinical pattern with Th1and Th17 cells subsets

Methods:  Patients with ERA (according to ILAR criteria) were included in a cross sectional study. Disease activity measures were collected in random visits: active joint count (AJ), pain score (0-10), active enthesitis (AE), sacroiliac pain (SIP) , lumbar pain (LP),lumbar limitation (LL) by Schöber´s test, wellbeing according to the patient using a visual analogue scale (VASp, 0-10), disease activity according to the physician (VASphy), JADAS-10, JSpADA, and ESR were evaluated. Patients were classified based on the articular pattern (peripheral and non-peripheral) depending on the presence or absence of AJ and/or AE. Functional capacity by CHAQ. Presence of radiologic sacroiliitis (MRI/X-rays) and treatment were recorded. Th-17 and Th-1 cells were quantified by flow cytometry in PBMCs stimulated with PMA/IO. Age-matched healthy children without disease or medication were recruited as normal control. Statical analysis:Mann-Whitney U test and correlation tests.

Results:  29 patients (90 % M) fulfilled inclusion criteria. HLA-B27 was positive in 13 (45%). Median age was 12 years and disease duration was 2.1 years at observation. Activity and functional measures were (medians): AJ 1, pain 0.25, VASp 0.5, VASphy 1, JADAS-10 7, JSpADA 1.75, ESR 15 mm/h; CHAQ ≥ 0.5 occurred in 8 patients (27%). AE was present in 1 (3%), SIP in 7 (24 %), LP in 6 (21%), and LL in 12 (41%) children. Nineteen (65%) patients showed JADAS >1 and 21 (76%) JSpADA>0. Radiologic sacroilitis was recorded in 21(72%) children. Fourteen (48%) patients were treated with TNFi. Th1cell percentage in ERA was 8.5±3.4% (range, 4-17.4) while healthy controls was 5.8±3.8% (range, 1.2-14.2), p=0.023. Th17cell% in ERA was 0.90±0.44(range, 0.39-2.34%) while controls was 0,55±0.38 (range, 0,17-1,61%); p=0.004. There was no difference between T-cells and active/inactive disease according scores. Eighteen (62%) children showed peripheral pattern, while 11(38%) exhibited non-peripheral. Peripheral and non-peripheral groups showed Th17% cells 0.90(0.39-1.74) vs 1.14(0.64-2.44) respectively(p=0.018).Significant correlations with Th1: AJ (r=0.45 p=0.004) and with Th17: LP (r=0.83 p=0,0001), LL (r=0.47 p=0.03).

Conclusion:

Th1 and Th17 cells subsets were significantly higher in ERA compared with healthy controls. However, T-cells showed no significant difference between patients with active versus inactive disease.Interestingly, non-peripheral pattern showed higher Th17% cells with respect to patients with peripheral disease pattern. ERA with axial arthritis may benefit most from Th-17 blocking strategies.