Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients.

Salah Aref,Mohamed Mabed,Al Shaimaa Abd Elmaksoud,Mohamed Ayed,Sherin Abd Elaziz

doi:10.31557/apjcp.2020.21.11.3177

Salah Aref, Mohamed Mabed + Show 3 more

Open Access

https://doi.org/10.31557/apjcp.2020.21.11.3177

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Abstract

Backgrounds:Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods:Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results:No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.

Highlights

Toll-like receptors (TLRs) are a family of transmembrane receptors which play an important role in the host defense against microorganisms
This study aimed to investigate the association between Toll-like receptors 2; 4 (TLR2) and TLR4 polymorphism and the risk of acquiring severe infections, and impact on acute myeloid leukemia (AML) patient’s outcome
In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis

Summary

Introduction

Toll-like receptors (TLRs) are a family of transmembrane receptors which play an important role in the host defense against microorganisms. TLRs are mainly expressed in human immune-related cells such as monocytes, neutrophils, macrophages, dendritic cells, T cells, B cells and NK cells (Uematsu et al, 2006; Rybka et al, 2015). TLRs alert the immune system to infection by recognizing pathogen-associated molecular patterns derived from various microorganisms (Beutler et al, 2004a; Beutler et al, 2004b). TLRs 1, 2, 4, 5 and 6 are typical for bacterial products, TLRs 3, 7 and 8 are characteristic for viral infection and TLR9 is associated with bacterial and viral inflammatory response (Tsujimoto et al, 2008). TLR2 and TLR4 are two of the most studied TLRs to have an important role in the recognition of both bacterial and fungal pathogens (Netea, et al, 2007)

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