The role of TLR-2 and TLR-4 gene polymorphisms in the development of sepsis in children with severe burns
DOI:
https://doi.org/10.12775/JEHS.2022.12.04.012Keywords
burns, Toll- like receptors, TLR-2 Arg 753 Gln and TLR-4 Thr399 Ile genes, sepsis, MOD, children, SIRSAbstract
Recently, many studies are based on the study of innate immunity genes, namely the role of TLRs in the development of various diseases. Severe burn injury is characterized by the development of hyperimmune reactions, which further leads to the development of multiple organ complications and sepsis. The aim of our study was to identify the frequency and prognostic value of polymorphism of TLR-2 Arg753Gln and TLR-4 Thr399 Ile genes and their role in the development of sepsis and MOD in children with severe burns. Materials and methods: genetic analysis of TLR-2 Arg 753 Gln and TLR-4 Thr399 Ile gene polymorphisms was performed in children with severe and extremely severe burns (n = 22) who were treated in the anesthesiology department with intensive care beds. Results: as a result of the obtained data, the heterozygous genotype TLR-2 Arg 753 Gln was detected in 69.5% (n = 16), in 31.8% (n = 7) patients with burn injury polymorphism was not detected. In 13.6% (n = 3) cases, polymorphism was associated with sepsis and MOD. Sepsis and normal homozygous genotype were diagnosed in 4.5% (n = 1). Heterozygous genotype TLR-4 Thr399 Ile was observed in 18.2% (n = 4) patients, of which only 4.5% (n = 1) patients had polymorphism associated with sepsis and MOD. Analysis of the association of TLR 2 genotypes and markers of acute inflammation revealed statistically significant differences between the heterozygous TLR 2 Arg 753 Gln genotype and C-reactive protein (CRP) levels in the blood of patients on day 3 of burn disease. Conclusions: The study of the role of innate immune system genes is promising in predicting the development of sepsis and complications in severe burns and requires further careful study.
References
. Hari A, Flach TL, Shi Y, Mydlarski PR. Toll-like receptors: role in dermatological disease. Mediators of inflammation. 2010 Oct; 2010.
O'Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7: 353–364, 2007.
G. Hahm, J. J. Glaser, and E. A. Elster, “Biomarkers to predict wound healing: the future of complex war wound management,” Plastic and Reconstructive Surgery, vol. 127, pp. 21S–26S, 2011.
L. J. McGhan and D. E. Jaroszewski, “The role of toll-like receptor-4 in the development of multi-organ failure following traumatic haemorrhagic shock and resuscitation,” Injury, vol. 43, no. 2, pp. 129–136, 2012.
El-Zayat SR, Sibaii H, Mannaa FA. Toll-like receptors activation, signaling, and targeting: an overview. Bulletin of the National Research Centre. 2019 Dec; 43(1):1-2.
Assenzio B, Martin-Conte EL. Cellular Mechanisms of MOF during Severe Sepsis and Septic Shock. INTECH Open Access Publisher; 2012 Feb 10.
Hernandez-Sancen P, Maldonado-Bernal C. Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer. Genes & Immunity. 2014 Jun;15(4):199-209.
Lei HE, Maohu LI, Wensheng FA, Yunxi LI, Jijiang SU, Yubin XI, Ning JI. Association of Single Nucleotide Polymorphisms in Toll-like Receptors with Acinetobacter baumanii Infectionin a Chinese Population. Iranian journal of public health. 2016 Jan;45(1):20
Zhao H, Perez JS, Lu K, George AJ, Ma D. Role of Toll-like receptor-4 in renal graft ischemia-reperfusion injury. American Journal of Physiology-Renal Physiology. 2014 Apr 15;306(8):F801-11.
Yuan FF, Marks K, Wong M, Watson S, de Leon E, McIntyre PB, Sullivan JS Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection. Immunol Cell Biol. 2008 Mar-Apr; 86(3):268-70.
. Gluba A, Banach M, Hannam S, Mikhailidis DP, Sakowicz A, Rysz J. The role of Toll-like receptors in renal diseases. Nat Rev Nephrol 6: 224–235, 2010.
Boiko JR, Borghesi L. Hematopoiesis sculpted by pathogens: Toll-like receptors and inflammatory mediators directly activate stem cells. Cytokine. 2012 Jan 1;57(1):1-8.
Navarini AA, Lang KS, Verschoor A, et al. Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections. Proc Natl Acad Sci U S A 2009;106:7107-12. 10.1073/pnas.0901162106 .
Assenzio B, Martin-Conte EL. Cellular Mechanisms of MOF during Severe Sepsis and Septic Shock. INTECH Open Access Publisher; 2012 Feb 10.
Bouhemad B, Nicolas-Robin A, Arbelot C, Arthaud M, Feger F, Rouby JJ. Acute left ventricular dilatation and shock-induced myocardial dysfunction. Crit Care Med 2009;37:441-447.
Streck EL, Comim CM, Barichello T, Quevedo J. The septic brain. Neurochem Res 2008;33:2171-2177.
Wischmeyer PE. Malnutrition in the acutely ill patient: is it more than just protein and energy? S Afr J Clin Nutr. 2011;24:1–7.
Newling M, Sritharan L, van der Ham AJ, Hoepel W, Fiechter RH, de Boer L, Zaat SA, Bisoendial RJ, Baeten DL, Everts B, den Dunnen J. C-reactive protein promotes inflammation through FcγR-induced glycolytic reprogramming of human macrophages. The Journal of Immunology. 2019 Jul 1;203(1):225-35.
Tsimogiannis KE, Tellis CC, Tselepis AD, Pappas-Gogos GK, Tsimoyiannis EC, Basdanis G. Toll-like receptors in the inflammatory response during open and laparoscopic colectomy for colorectal cancer. Surgical endoscopy. 2012 Feb;26(2):330-6.
Di S, Wang Y, Sun L, Zhao H, Guo L. The value of TLR-4, CRP, PCT and WBC levels in assessing the diagnosis and prognosis of sepsis patients. International journal of clinical and experimental medicine. 2020 Jan 1;13(12):9419-28.
Haider DG, Leuchten N, Schaller G, Gouya G, Kolodjaschna J, Schmetterer L, Kapiotis S, Wolzt M. C-reactive protein is expressed and secreted by peripheral blood mononuclear cells. Clinical & Experimental Immunology. 2006 Dec;146(3):533-9.
Newling M, Sritharan L, Baeten D, Den Dunnen J. P080 C-reactive protein: not only a marker, but also a cause of inflammation through metabolic reprogramming of human macrophages. Annals of the Rheumatic Diseases. 2018 Mar 1;77: A47.
Yurko K, Kozko V, Solomennik A, Bondar O, Sokhan A, Gavrylov A. The role of polymorphism asp299gly of the gene tlr 4 in patients co-infected with hiv/hcv. Georgian medical news. 2018 jul 1(280-281):138-41.
AbdAllah NB, Toraih EA, Al Ageeli E, Elhagrasy H, Gouda NS, Fawzy MS, Helal GM. MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis. Scientific Reports. 2021 Jun 28;11(1):1-4.
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