Toll-like receptor-8 mRNA expression as a predictor of enterocolitis in hirschsprung disease: a cross-sectional study

Abstract

Introduction: Hirschsprung-associated enterocolitis (HAEC) is an inflammatory intestinal condition occurring in patients with Hirschsprung disease (HD). While the exact pathogenesis remains unclear, factors such as intestinal mucosal barrier injury, abnormal immune responses, and pathogenic infections contribute to HAEC. Toll-like receptors (TLRs) 7 and 8 are key in viral recognition and correlate with intestinal mucosal inflammation. In particular, TLR-8 contributes to antiviral responses, and chronic inflammation, and can be targeted with adjuvants. This study investigates the relationship between TLR-8 mRNA expression and enterocolitis in HD. Methods: This cross-sectional study utilized simple random sampling. Histopathological analysis of colon samples from HD patients was used to assess enterocolitis severity, and RT-PCR quantified TLR-8 mRNA expression. HD diagnosis was confirmed via rectal biopsy, and enterocolitis was graded using Teitelbaum’s classification. Results: The study included 29 patients with an average age of 4.8 years. TLR-8 mRNA expression averaged 8.5 (fold change), ranging from 6.5 to 13.8. Subjects were divided into low (≤8.1) and high (>8.1) expression groups, with 15 (51.7%) and 14 (48.3%) patients, respectively. Enterocolitis severity distribution was 22 (75.9%) normal, 1 (3.4%) grade II, 4 (13.8%) grade III, and 2 (6.9%) IV. Conclusion: There is a significant association between TLR-8 mRNA expression and the incidence of enterocolitis in patients with HD. The authors found that increased TLR-8 mRNA expression in HD patients resulted in a twofold higher risk of enterocolitis. Altogether, our data indicates the potential for TLR-8 mRNA expression in biopsies as an indicator of the risk of enterocolitis development in patients with HD.