Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia

M A Karnaushkina; A S Guryev; K O Mironov; E A Dunaeva; V I Korchagin; O Yu Bobkova; I S Vasilyeva; D V Kassina; M M Litvinova

doi:10.17691/stm2021.13.3.06

Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia

Sovrem Tekhnologii Med. 2021;13(3):47-53. doi: 10.17691/stm2021.13.3.06. Epub 2021 Jun 28.

Authors

M A Karnaushkina¹, A S Guryev², K O Mironov³, E A Dunaeva⁴, V I Korchagin⁴, O Yu Bobkova⁵, I S Vasilyeva⁶, D V Kassina⁷, M M Litvinova⁸

Affiliations

¹ Professor, Department of Internal Diseases with a Course of Cardiology and Functional Diagnostics named after Academician V.S. Moiseev; Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow, 117198, Russia.
² Senior Researcher, Research Laboratory; Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, 61/2-1 Schepkina St., Moscow, 129110, Russia.
³ Head of the Research Group for the Development of New Methods for Identifying Genetic Polymorphisms; Central Research Institute of Epidemiology of the Federal Service on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), 3а Novogireevskaya St., Moscow, 111123, Russia.
⁴ Researcher, Research Group for the Development of New Methods for Identifying Genetic Polymorphisms; Central Research Institute of Epidemiology of the Federal Service on Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), 3а Novogireevskaya St., Moscow, 111123, Russia.
⁵ PhD Student, Department of Hospital Therapy No.2; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya St., Moscow, 119991, Russia.
⁶ Assistant, Department of Hospital Therapy No.2; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya St., Moscow, 119991, Russia.
⁷ Researcher, Research Laboratory; Moscow Regional Research Clinical Institute named after M.F. Vladimirsky, 61/2-1 Schepkina St., Moscow, 129110, Russia.
⁸ Associate Professor, Department of Medical Genetics; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya St., Moscow, 119991, Russia; Geneticist, Center for Personalized Medicine; Moscow Clinical Scientific Center named after A.S. Loginov, Moscow Healthcare Department, 86 Shosse Entuziastov, Moscow, 111123, Russia.

Abstract

The aim of the study was to determine the molecular genetic prognostic criteria for the severity of the course pneumonia based on the analysis of the association of genetic polymorphism in toll-like receptors with the severity of NETosis.

Materials and methods: The study included 38 patients with the main diagnosis of community-acquired pneumonia with a severe course. All the patients underwent standard clinical laboratory examinations, computed tomography of the thoracic organs, microbiological examination of blood and tracheobronchial aspirate. The level of neutrophilic extracellular traps (NETs) in blood smears was determined on the 1^st-2^nd and 5^th-7^th days of hospitalization. Genotyping of rs5743551 (TLR1), rs5743708 (TLR2), and rs4986790 (TLR4) polymorphic loci was performed by pyrosequencing.

Results: The level of NETs on the 1^st day of admission was statistically significantly lower in heterozygous and homozygous carriers of rs4986790 (TLR4) polymorphism (AG and GG genotypes) compared with patients with the wild-type genotype (AA genotype) (p<0.05). When comparing the number of NETs with genotypes for rs5743708 (TLR2) and rs5743551 (TLR1) polymorphisms, no statistically significant correlation was found (p>0.05). The study of the NET level in dynamics demonstrated a decrease in the NETosis activity of neutrophils during the first week of hospitalization (p<0.05). The presence of the G allele in the patient's genotype for rs5743551 (TLR1) polymorphism increases the risk of a poor outcome of the disease (p<0.0001) (OR=20.3; 95% CI (4.3-135.0)).

Conclusion: The obtained data suggest that level of NETs is a marker of the activity of neutrophils which are closely related to the studied genetic polymorphisms, and affects the prognosis of the pneumonia outcome.

Keywords: TLR1; TLR2; TLR4; gene polymorphism; neutrophilic extracellular traps; pneumonia.

MeSH terms

Case-Control Studies
Extracellular Traps*
Genetic Predisposition to Disease*
Humans
Pneumonia* / diagnosis
Polymorphism, Single Nucleotide
Prognosis
Toll-Like Receptor 1 / genetics
Toll-Like Receptor 2 / genetics
Toll-Like Receptor 4 / genetics
Toll-Like Receptors* / genetics

Substances

Toll-Like Receptor 1
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptors

Grants and funding

Research funding. The work did not receive any financial support.