IL-36 has been implicated in the pathogenesis of spondyloarthropathies (SpA) like psoriasis and inflammatory bowel disease. Enthesitis related arthritis (ERA) category of juvenile idiopathic arthritis is a form of juvenile SpA, however no data is available on the role of IL-36 in this disease. IL-36α, β, γ and IL-36R mRNA expression in blood and synovial fluid mononuclear cells and IL-36α, γ, IL-36Ra, IL-6 and IL-17 levels were measured in serum and synovial fluid (SF). IL-36γ production by fibroblast like synoviocytes (FLS) upon stimulation with pro-inflammatory cytokines and its effect on FLS were also studied. mRNA levels of IL-36α, IL-36γ and IL-36R were increased in PBMCs of ERA patients as compared to healthy controls however only IL-36γ was measurable in serum of one third of patients. In SFMCs, all 4 mRNA were detectable but were lower than RA patients. SF IL-36γ levels correlated with disease activity score (r=0.51, p< 0.0001), SF IL-6 (r=0.4, p= 0.0063) and IL-17 levels (r=0.57, p=0.0018). Pro-inflammatory cytokines increased expression of IL-36γ and IL-6 in FLS cultures. SFs from 5 ERA patients also increased expressions of IL-36γ and IL-6 in FLS which could be blocked by using IL-36Ra. This suggests that pro-inflammatory cytokines aid in upregulation of IL-36γ which in turn may upregulate expression of IL-6. This might lead to a positive feedback loop of inflammation in ERA. Association of SF levels of IL-36γ with disease activity further supports this possibility. IL-36Ra based therapy may have a role in ERA.
Objectives Long-term functional outcomes in enthesitis-related arthritis (ERA) is limited from developing countries. We assessed the clinical and genetic factors that predicted the long-term functional outcome in ERA. Methods Patients with ERA having ≥5 years of disease and > 16 years of age were included in this cross-sectional study. Data on clinical features within 6 months of disease onset was collected from hospital records. Bath indices, HAQ-DI, and WHO-QOL were assessed at last visit. Poor functional outcome (PFO) was defined as BASFI > 1.5 or HAQ-DI > 1. Persistent disease activity (PDA) was defined as BASDAI ≥ 4. ERAP-1 and IL23R SNP genotyping was done by TaqMan method and HLA-B27 by PCR. Results 181 patients [170-male, age of disease onset 12.5 (10–15) years, disease duration 7 (5–11) years] were recruited. There was delay in diagnosis of 3 (1–5) years. The median ASDAS-ESR, BASDAI, HAQ-DI, and BASFI at inclusion were 2.6(1.8–3.6), 2.6(1–5.2), 0.5(0–0.5) and 1.6(0.3–3.2) respectively. BASFI and HAQ-DI correlated with ASDAS-ESR, ASDAS-CRP and WHO-QOL-BREF. Those with PFO (n = 98) had a longer delay in diagnosis (4 vs 2 years, p< 0.001), lower prevalence of arthritis at onset (OR = 0.3,95%CI : 0.1–0.8), higher prevalence of ERAP1(rs27044) allele C (OR = 7.2, 95%CI : 1.5–33.7), and higher disease activity currently. Delay in diagnosis (OR = 1.2; 95%CI : 1.08–1.4) was the sole predictors of PFO in multivariate analysis. One-third of patients had PDA. Tarsitis at disease onset was the sole predictor of PDA (OR = 2.3; 95%CI : 1.009–5.4). Conclusions Poor functional outcome was seen in one-half of JIA-ERA in the long-term and was associated with active disease with delay in diagnosis as its sole predictor.
Background/Aims Long-term functional outcomes in enthesitis-related arthritis (ERA), is limited from developing countries. We assessed the clinical and genetic factors that predicted the long-term functional outcome in ERA. Methods Patients with ERA having >5 years of disease and > 16 years of age were included in this cross-sectional study. Data on clinical features within 6 months of disease onset was collected from hospital records. Bath indices, HAQ-DI, and WHO-QOL were assessed at last visit. Poor functional outcome (PFO) was defined as BASFI>1.5 or HAQ-DI>1. Persistent disease activity (PDA) was defined as BASDAI>4. ERAP-1 and IL23R SNP genotyping was done by TaqMan method and HLA-B27 by PCR. Results 181 patients [170-male, age of disease onset 12.5 (10-15) years, disease duration 7 (5-11) years] were recruited. There was delay in diagnosis of 3 (1-5) years. The median ASDAS-ESR, BASDAI, HAQ-DI, and BASFI at inclusion were 2.6 (1.8-3.6), 2.6 (1-5.2), 0.5 (0-0.5) and 1.6 (0.3-3.2) respectively. BASFI and HAQ-DI correlated with ASDAS-ESR, ASDAS-CRP and WHO-QOL-BREF. Those with PFO (n = 98) had a longer delay in diagnosis (4 vs 2 years, p < 0.001), lower prevalence of arthritis at onset (OR = 0.3, 95%CI:0.1-0.8), higher prevalence of ERAP1(rs27044) allele C (OR = 7.2, 95%CI:1.5-33.7), and higher disease activity currently. Delay in diagnosis (OR = 1.2; 95%CI:1.08-1.4) was the sole predictors of PFO in multivariate analysis. One-third of patients had PDA. Tarsitis at disease onset was the sole predictor of PDA (OR = 2.3; 95%CI:1.009-5.4). Conclusion Poor functional outcome was seen in one-half of JIA-ERA in the long-term and was associated with active disease with delay in diagnosis as its sole predictor. Disclosure N. Ravichandran: None. S. Guleria: None. N. Mohindra: None. A. Aggarwal: None.
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