Lipid and immune profiles in children with systemic juvenile idiopathic arthritis: a case-control study with paired longitudinal comparison of disease activity.

Background: Systemic juvenile idiopathic arthritis (SoJIA) lacks specific biomarkers for objective disease activity assessment. Conventional inflammatory markers have limited accuracy for monitoring disease fluctuation. Few studies have integrated lipid metabolic and immune parameters to support SoJIA activity assessment, underscoring the need for simple and efficient biomarker combinations. This study aims to characterize differences in immune parameters between children with active SoJIA and healthy controls; compare the lipid profiles among children with active SoJIA, the same children in remission, and healthy controls; and explore the ability of these parameters to discriminate between disease states. Methods: This single-center retrospective case-control study included 63 treatment-naive children newly diagnosed SoJIA (PRINTO 2018 criteria). Remission was defined by ACR/PRINTO criteria, with normal C-reactive protein (CRP) ≤10 mg/L and erythrocyte sedimentation rate (ESR) ≤20 mm/h. Forty age- and sex-matched healthy children served as controls. Blood was collected after an overnight fast. Immune, cytokine, lipid, and inflammatory markers were measured using standardized clinical laboratory procedures. Cellular immune markers (CD3⁺, CD4⁺, CD8⁺, CD16⁺CD56⁺, CD19⁺), cytokines [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), soluble interleukin-2 receptor (sIL-2R)], humoral immune indicators [immunoglobulin G (IgG), immunoglobulin M (IgM), complement component 3 (C3), complement component 4 (C4)], lipid parameters, CRP, and ESR were measured. The atherogenic index (AI) was calculated. Results: Compared with healthy controls, children with active SoJIA had significantly higher levels of C3, C4, IL-6, IL-10, TNF-α, CRP, and ESR; higher proportions of CD3⁺ and CD4⁺ T cells; and lower B cells than controls (all P<0.05). Both active and remission patients had lipid abnormalities (lower HDL-C, higher TG and AI), more pronounced during active disease. Total cholesterol (TC) was elevated only in the active group (all P<0.05). Joint swelling and fever were more frequent during active disease than during remission (P<0.05). A CRP + IL-6 + AI model distinguished active SoJIA from controls with exploratory ability (73.0% sensitivity, 95.0% specificity). AI + TG distinguished active from remission disease (area under the curve =0.8650). Conclusions: Active SoJIA shows prominent immune-inflammatory dysregulation and lipid abnormalities that partially improve with remission. The CRP + IL-6 + AI model showed exploratory ability to distinguish active SoJIA from health, whereas AI alone demonstrated exploratory potential for evaluating disease activity. Adding TG did not significantly improve performance (DeLong test, P=0.80). As only healthy controls were included without disease-mimic groups and models lacked independent validation, these findings are hypothesis-generating and cannot support clinical differential diagnosis. Prospective multicenter studies that include appropriate disease-control groups and independent validation cohorts are needed.