Advances in non-invasive biomarkers for pediatric inflammatory bowel disease diagnosis

Table 1 Key biomarkers for diagnosing pediatric inflammatory bowel disease

Biomarker	Type	Role in diagnosis	Disease subtypes	Diagnostic performance	Notes
Fecal calprotectin	Fecal marker	Detects intestinal inflammation; differentiates IBD from non-IBD conditions	Crohn’s disease, ulcerative colitis	High sensitivity and specificity (commonly > 80%-90%)	Widely used for screening, monitoring disease activity, and relapse prediction
S100A12	Fecal marker	Inflammatory marker for pediatric IBD diagnosis	Crohn’s disease, ulcerative colitis	Sensitivity approximately 95%, specificity approximately 97%	Higher specificity for intestinal inflammation compared with CRP
Leucine-rich alpha-2 glycoprotein	Serum marker	Reflects intestinal inflammatory activity	Crohn’s disease, ulcerative colitis	Moderate to high diagnostic accuracy; superior to CRP	Useful adjunct marker when fecal testing is limited
CRP	Serum marker	Acute-phase reactant for systemic inflammation	Crohn’s disease, ulcerative colitis	Moderate sensitivity; low disease specificity	Non-specific marker; influenced by infections and extraintestinal inflammation
Proteomic markers	Serum/plasma proteins	Identifies protein signatures distinguishing IBD subtypes	Crohn’s disease, ulcerative colitis	AUC > 0.90 in selected pediatric studies	Promising for disease stratification; limited routine availability
ASCA	Serological marker	Supports differentiation of Crohn’s disease	Crohn’s disease	Moderate sensitivity and specificity	Limited diagnostic utility as a standalone test
Perinuclear anti-neutrophil cytoplasmic antibodies	Serological marker	Supports differentiation of ulcerative colitis	Ulcerative colitis	Moderate sensitivity and specificity	Often interpreted in combination with ASCA
DNA methylation markers	Epigenetic marker	Provides diagnostic and prognostic information	Crohn’s disease, ulcerative colitis	AUC approximately 0.90-0.94 (IBD vs controls)	Emerging tools; currently research-based
MicroRNA signatures	Serum/plasma marker	Predicts disease activity and relapse risk	Crohn’s disease, ulcerative colitis	High sensitivity; AUC up to approximately 0.90	Potential role in treatment response prediction
Gut microbiome profiles	Microbiome marker	Differentiates IBD subtypes based on microbial alterations	Crohn’s disease, ulcerative colitis	AUC approximately 0.95 in selected cohorts	High inter-cohort variability; limited standardization

ASCA: Anti-saccharomyces cerevisiae antibodies; IBD: Inflammatory bowel disease; CRP: C-reactive protein; AUC: Area under the curve.