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PubMed2026

Complement Activation Linked to Type II Interferon Signaling in Still Disease.

OBJECTIVE: Still disease (SD) is an autoinflammatory syndrome characterized by innate immune dysregulation. Although complement can drive inflammation, its involvement in SD remains to be defined. Thus, we aimed to assess complement activation in SD. METHODS: Complement was assessed using transcriptomic, proteomic, and in vitro approaches. RNA sequencing of monocytes was performed in healthy donors (n = 15), those with nonsystemic juvenile idiopathic arthritis (JIA; n = 8), patients with SD at onset (n = 19) and remission (n = 18), and those with macrophage activation syndrome (n = 2). Whole-blood NanoString analysis of complement and interferon (IFN)-related gene expression was conducted in patients with SD (active n = 41, inactive n = 33) and JIA (n > 600). Complement products and inflammatory mediators were measured by Luminex and enzyme-linked immunosorbent assay. Functional complement activity was evaluated in SD (active n = 30, inactive n = 67) and JIA sera (n = 12). In vitro assays examined monocytic C1q induction and complement-mediated CD8+ T cell activation. RESULTS: Transcriptomic analysis of monocytes from patients with SD at onset revealed enrichment of the complement cascade compared with patients in remission (adjusted P = 3.7 × 10-36), ranking among the top 10 up-regulated pathways. Classical complement genes (C1QB/C1QC) were markedly up-regulated in onset SD compared with patients with remission SD and JIA. Patients with active SD showed increased C1q, C3a, C5a, and terminal complement complex protein levels, with enhanced functional classical complement activity. Whole-blood C1QB/C1QC expression correlated with IFN-related markers, including interleukin-18, CXCL9, and CXCL10. Recombinant IFN-γ induced monocytic C1q, whereas C1q enhanced IFN-γ production by CD8+ T cells, supporting a feed-forward loop. CONCLUSION: SD is characterized by complement activation with marked up-regulation of C1q, which is closely linked to IFN-γ/type II signaling.

Journal Article↗

PubMed2026

Effect of Time to Start of Biologic Therapy on Treatment Response in Childhood Arthritis: Results From the UCAN CAN-DU Cohort.

OBJECTIVE: To estimate the effect of time from symptom onset to start of biologic treatment on achieving inactive arthritis within six months in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: The international UCAN CAN-DU study prospectively enrolled patients with JIA across Canada and the Netherlands. A nested cohort study was performed and biologic-naive patients with nonsystemic JIA were included at the start of biologic therapy. The primary outcome was inactive arthritis at six months. Demographics, disease-related parameters, and treatment response were compared using (non)parametric tests among early (time symptom onset to biologic start: 0-6 months), intermediate (7-12 months), and late (13-24 months) treatment groups. A logistic regression model analyzed the effect of time to biologic start on the response at six months, adjusting for active joint count and physician global assessment. A graphical representation of the model was created. RESULTS: One hundred and thirty children with JIA were included (early: n = 35; intermediate: n = 46; late: n = 49), 66% were female, and the median age at symptom onset was 11.0 years. The proportion of patients that reach inactive arthritis in the early starters (83%) was significantly higher than in late starters (57%). For each month of delay to the start of biologic treatment, the adjusted odds of having active arthritis after six months of therapy was 1.09 (interquartile range: 1.02-1.17, P = 0.009). CONCLUSION: Early start of biologic therapies in patients with JIA was associated with a higher proportion of patients reaching inactive arthritis within six months, suggesting a window of opportunity to control disease activity.

Humans↗