Intestinal Fatty Acid Binding Protein Levels in Pediatric Celiac Patients in Transition From Active Disease to Clinical and Serological Remission

**Background:** Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis traditionally relies on duodenal biopsies and elevated serological markers like tissue transglutaminase IgA (TTG-IgA). However, serology has limited sensitivity and specificity for detecting persistent villous atrophy during follow-up. Intestinal fatty acid binding protein (I-FABP) is a cytosolic protein released from damaged enterocytes, and prior studies suggest it may reflect mucosal damage more reliably. This study aimed to prospectively evaluate I-FABP levels in pediatric CD patients at diagnosis and after 6 months of gluten-free diet (GFD) compared to non-celiac controls.

**Methods:** A prospective observational case-control study was conducted at Schneider Children’s Medical Center of Israel. Inclusion criteria for the CD group: children <17 years with clinical suspicion of CD, elevated TTG-IgA (≥3 times upper limit of normal [ULN]), and duodenal biopsy confirming CD (Marsh ≥2). Controls were children undergoing endoscopy for nonspecific abdominal pain with negative celiac serology and normal histology (Marsh 0). Exclusion criteria included conditions known to elevate I-FABP (e.g., inflammatory bowel disease, bowel ischemia, recent surgery, NSAID use, intense physical activity). Serum I-FABP was measured at diagnosis (before endoscopy) and after 6 months of GFD using a commercial ELISA kit. TTG-IgA levels were recorded as multiples of ULN. GFD adherence was assessed using the modified Biagi questionnaire. Statistical analysis used Pearson correlation, AUC, and Mann-Whitney U tests; p<0.05 was significant.

**Key Results:** 35 CD patients (10 Marsh 3B, 25 Marsh 3C) and 32 controls were included. Gender distribution was similar (21.8% male controls vs. 31.4% CD, p=0.4). CD patients were younger (mean 7.8±3 vs. 12±4 years, p<0.05). H. pylori was less frequent in CD (8.5% vs. 32.3%, p<0.05). At diagnosis, median TTG-IgA in CD was 19.3 times ULN (range 3.8–111.1). Median I-FABP was significantly higher in CD (641.7 pg/mL, range 356.2–1381) vs. controls (334 pg/mL, range 171.43–791; p<0.05). Among CD patients, those with TTG-IgA 3–10 times ULN had median I-FABP 432.2 pg/mL, while those with >10 times ULN had median 796.2 pg/mL (p<0.05). A weak negative correlation was found between I-FABP and age (Spearman’s rho −0.46, p<0.05). I-FABP did not differ by H. pylori status in controls (HP+ 271.6 vs. HP− 365.4 pg/mL, p=0.17). At 6-month follow-up, 13/35 CD patients had samples; 12/13 completed Biagi questionnaires (median score 4, indicating high adherence). Median TTG-IgA dropped to 2 times ULN (range 0.3–13.7). Median I-FABP decreased significantly to 268.2 pg/mL (range 171–468) vs. 641.7 pg/mL at diagnosis (p<0.05). 85% of patients reported being asymptomatic.

**Clinical Implications:** This study demonstrates that I-FABP levels are elevated in pediatric CD at diagnosis and correlate with serological disease activity. After 6 months of GFD, I-FABP levels decreased significantly, reaching levels comparable to non-celiac controls, paralleling serological improvement and reported adherence. These findings suggest I-FABP could serve as a noninvasive biomarker for both diagnosis and monitoring of mucosal healing in pediatric CD, potentially reducing the need for repeat endoscopy. However, limitations include small sample size, loss to follow-up, and lack of repeat biopsies to confirm histological correlation. Future larger studies with paired biopsies are needed to validate I-FABP as a routine clinical tool.