The predictive value of the ratio of multi-dimensional inflammatory biomarkers in pediatric diseases from the perspective of pro-inflammatory/anti-inflammatory balance: a systematic review.
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BACKGROUND: Imbalance of immune homeostasis, particularly the dysregulation of pro-inflammatory/anti-inflammatory balance, is a core pathological mechanism in many acute and chronic pediatric diseases. Traditional single inflammatory biomarkers have limitations in disease prediction, clinical evaluation, and prognostic stratification, as they cannot reflect the overall dynamic balance of the immune network. This systematic review aimed to evaluate the predictive value of multi‑dimensional inflammatory biomarker ratios centered on pro‑inflammatory/anti‑inflammatory balance in pediatric inflammatory diseases, and to clarify their classification and clinical application strategies. METHODS: We performed this systematic review in accordance with the PRISMA guidelines. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP Chinese Science and Technology Journal Database databases from database inception to December 31, 2025. Eligible studies were original studies that focused on multi-dimensional inflammatory biomarker ratios in children aged ≤18 years. We excluded animal studies, studies involving only adult populations, low-quality studies, conference abstracts, case reports, and irrelevant correspondence. Two independent reviewers conducted literature screening, data extraction, and methodological quality assessment using standard tools, with 32 articles finally included in this systematic review. RESULTS: We categorized multi-dimensional inflammatory biomarker ratios into two classes: Class A [cytokine-based ratios, e.g., interleukin (IL)-6/IL-10, tumor necrosis factor-α (TNF-α)/IL-10, IL-17A/IL-10, IL-1β/IL-1 receptor antagonist (IL-1Ra)], which have high specificity for reflecting molecular immune balance; and Class B (systemic inflammatory ratios derived from routine laboratory tests, e.g., neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Systemic Immune-Inflammation Index, C-reactive protein-to-albumin ratio), which have high accessibility in clinical practice for rapid screening. Compared with single inflammatory biomarkers, these multi-dimensional ratios demonstrated superior predictive performance in disease prediction, severity assessment, and prognosis of pediatric sepsis, Kawasaki disease, juvenile idiopathic arthritis, and pediatric multisystem inflammatory syndrome. CONCLUSIONS: Multi-dimensional inflammatory biomarker ratios, centered on the pro-inflammatory/anti-inflammatory balance, overcome the limitations of single inflammatory markers. In clinical practice, Class A ratios facilitate precise immune subtyping and targeted therapy, while Class B ratios facilitate early screening and severity stratification of pediatric inflammatory diseases. The combined application of both classes can establish a stratified and precise diagnosis and treatment framework for pediatric inflammatory diseases. Future research should establish pediatric reference ranges for these ratios, conduct large-scale prospective validation studies, and integrate artificial intelligence and point-of-care testing (POCT) technologies to promote the advancement of individualized pediatric care.