Correlation Between Non-Invasive Biomarkers and Histological Healing in Children with Celiac Disease: Role of Cytokines, Intestinal Fatty Acid-Binding Protein, and Tissue Transglutaminase Antibodies.
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PURPOSE: Data on treatment response in children with celiac disease (CeD), particularly with respect to changes in tissue transglutaminase IgA antibodies (tTGA-IgA), cytokines, intestinal fatty acid-binding protein (I-FABP), and quantitative histology, remain limited. To evaluate the utility of non-invasive parameters (NIPs), including I-FABP, tTGA-IgA, and cytokines, as potential markers of mucosal recovery in pediatric CeD. METHODS: This single-center, prospective, observational follow-up study included children with newly diagnosed CeD. Blood and duodenal biopsy samples were obtained at baseline and after 1 year of follow-up. RESULTS: Seventy-nine children who underwent follow-up biopsy at 1 year were analyzed. Significant improvements were observed in anthropometric measures, histological parameters, tTGA-IgA levels, cytokine profiles (tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], interleukin [IL]-15, IL-6, and IL-10), and I-FABP levels. tTGA-IgA showed strong correlations with histological indices, including intraepithelial lymphocyte (IEL) count (r=0.554, p<0.001), villous height (r=-0.557, p<0.001), crypt depth (r=0.553, p<0.001), and villous-to-crypt ratio (VCR; r=-0.561, p<0.001). TNF-α demonstrated weak correlation with crypt depth (r=0.24, p=0.04) and VCR (r=-0.22, p=0.05). IL-15 levels (r=0.34, p=0.003) and Δcycle threshold (Ct) scores correlated with IEL counts (r=-0.22, p=0.048). IFN-γ ΔCt scores also correlated with IEL counts (r=-0.34, p=0.001). CONCLUSION: Among the NIPs evaluated, tTGA-IgA showed the strongest correlation with mucosal recovery at 1 year. TNF-α, IL-15, and IFN-γ demonstrated weaker but significant correlations and may have the potential as adjunctive NIP of mucosal healing in pediatric CeD.