Additional file 4: of Childhood-onset granulomatosis with polyangiitis and microscopic polyangiitis: systematic review and meta-analysis

Subgroup analysis. (DOCX 21 kb

Additional file 3: of Clinical features of children with enthesitis-related juvenile idiopathic arthritis / juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre

Figure S2. Biological therapy: time to introduction and remission rate. Disease duration before introduction of a first line of biological therapy (years). Remission rate after introduction of a biological therapy (years). Remission was defined as the absence of any articular involvement (both peripheral and axial) and any enthesial involvement for at least six months. (DOCX 104 kb

Additional file 2: of Clinical features of children with enthesitis-related juvenile idiopathic arthritis / juvenile spondyloarthritis followed in a French tertiary care pediatric rheumatology centre

Figure S1. Evolution of the prevalence of inflammatory back pain. Inflammatory back pain was defined as proposed by the ASAS in 2009 [39]. Insidious onset. Improvement with exercise. No improvement with rest. Pain at night. (DOCX 63 kb

DataSheet_1_Targeting the chemokine receptor CXCR4 with histamine analog to reduce inflammation in juvenile arthritis.docx

IntroductionAmong immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of inflammatory factors contribute to the damage of bone-cartilage joints. Despite the moderate beneficial effect of current therapies and clinical trials, there is still a need for alternative strategies targeting monocytes to treat RA.MethodsTo explore such an alternative strategy, we investigated the effects of targeting the CXCR4 receptor using the histamine analog clobenpropit (CB). Monocytes were isolated from the blood and synovial fluids of JIA patients to assess CB's impact on their production of key inflammatory cytokines. Additionally, we administered daily intraperitoneal CB treatment to arthritic mice to evaluate its effects on circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, as indicators of disease progression.ResultsOur findings demonstrated that CXCR4 targeting with CB significantly inhibited the spontaneous and induced-production of key inflammatory cytokines by monocytes isolated from JIA patients. Furthermore, CB treatment in a mouse model of collagen-induce arthritis resulted in a significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, leading to a reduction in disease progression.DiscussionIn conclusion, targeting CXCR4 with the small amino compound CB shows promise as a therapeutic option for chronic and viral-induced inflammatory diseases, including RA. CB effectively regulated inflammatory cytokine production of monocytes, presenting a potential targeted approach with potential advantages over current therapies. These results warrant further research and clinical trials to explore the full therapeutic potential of targeting CXCR4 with CB-like molecules in the management of various inflammatory diseases.</p

Additional file 1: of Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy

Table S1 Definition of adapted ACR JIA response. Table S2 Genes with ≥3-fold differential expression between patients with SJIA and healthy controls, prior to canakinumab treatment. Table S3 List of independent ethics committees or institutional review boards (trial 1). Table S4 List of independent ethics committees or institutional review boards (trial 2). (DOCX 53 kb