IMMUNOLOGICAL DETERMINANTS OF THE RISK OF POSTOPERATIVE ENTEROCOLITIS IN CHILDREN WITH GIRSHPRUNG'S DISEASE
Keywords:
Hirschsprung disease, postoperative enterocolitis, immunological determinants, TLR4, zonulin, sCD14, CD4/CD8, sIgA, prognosis of complicationsAbstract
Postoperative enterocolitis in Hirschsprung's disease remains one of the most dangerous and frequent complications of surgical treatment, developing in 25-42% of patients. Despite the improvement of surgical methods, the pathogenesis of POEBG remains insufficiently studied, which limits the possibilities of early prediction and prevention. The purpose of the study is to assess the immunological determinants associated with the development of POEBG and to determine their prognostic significance. The study included 153 children with Hirschsprung's disease: 75 with POEBG and 78 without complications. A comprehensive assessment of congenital, adaptive, and mucosal immunity was conducted before and after surgery. It was established that children with POEBG are characterized by a decrease in the level of CD4+ lymphocytes, the CD4+/CD8+ index <1.2, pronounced activation of NK cells, an increase in IL-6 (2.8 times), TNF-α (2.3 times), a decrease in IL-10 (1.9 times), an increase in the expression of TLR4, the levels of zonulin and sCD14, as well as a significant deficiency of sIgA. An immunological prognostic scale based on five independent biomarkers has been proposed. The obtained data demonstrate the high prognostic significance of immune indicators and confirm the key role of neuroimmune imbalance and barrier dysfunction in the development of POEBG. The results allow for the inclusion of immunological monitoring in the postoperative observation standard.
References
Amiel J., Lyonnet S. Hirschsprung disease, associated syndromes, and genetics: A review. J. Med. Genet. 2001;38(11):729–739.
Heuckeroth R.O. Hirschsprung disease — integrating basic science and clinical medicine to improve outcomes. Nat. Rev. Gastroenterol. Hepatol. 2018;15(3):152–167.
Kapoor A., et al. Immune dysregulation and enterocolitis in children with Hirschsprung disease. J. Pediatr. Surg. 2020;55(4):604–610.
Cheng W., et al. Hirschsprung-associated enterocolitis: pathogenesis, diagnosis, and management strategies. Pediatr. Surg. Int. 2017;33(10):1047–1056.
Austin K.M. The pathogenesis of Hirschsprung-associated enterocolitis. Semin. Pediatr. Surg. 2012;21(4):319–327.
Frykman P.K., et al. Toll-like receptor pathways in Hirschsprung-associated enterocolitis. J. Pediatr. Surg. 2015;50(1):132–138.
Pini Prato A., et al. Long-term outcomes and risk factors of Hirschsprung-associated enterocolitis after pull-through surgery. Ann. Surg. 2019;270(3):610–618.
Yang M., et al. Zonulin as a biomarker of intestinal barrier dysfunction in pediatric surgical diseases. Clin. Chim. Acta. 2021;514:1–7.
Shen D.H., et al. Predictive value of inflammatory cytokines in postoperative enterocolitis in children with Hirschsprung disease. World J. Pediatr. 2020;16(3):262–269.
Schwengel D.A., et al. CD4/CD8 ratio disturbances and innate immune activation in complicated Hirschsprung disease. Pediatr. Res. 2016;80(5):745–752.
