Changes in the expression of genes encoding ACE2 and innate immunity molecules (TLR7, IFN-α, IL-1β, TNF) in elderly patients with COVID-19
AbstractIntroduction. The SARS-CoV-2 infection has placed a significant weight on the healthcare systems around the world. In this regard, the study of possible predictors of an unfavorable course and outcome of the disease, as well as the development of thrombotic complications, is an urgent and important task in the context of the ongoing circulation of SARS-CoV-2.
Aim. The aim of the work was to study the expression of genes encoding the ACE2, the innate immunity receptor TLR7, the cytokines IFN-α, IL-1β and TNF in peripheral blood leukocytes in elderly patients with COVID-19, as well as the association of the expression of these genes with the risk of thrombotic complications development, assessed by the level of D-dimer.
Material and methods. The study included 50 elderly patients (65–77 years old) with a confirmed diagnosis of COVID-19, the comparison group consisted of 15 persons (65–69 years old) without COVID-19. Gene expression was assessed by real-time PCR with reverse transcription in leukocytes obtained from peripheral blood.
Results. A significant decrease in ACE2 gene expression was shown in the main group compared to the group of healthy persons. Evaluation of innate immunity molecules showed an increase of the expression of the TLR7 and IFNA genes, as well as the TNF and IL1B genes, compared to the group of healthy persons. A special task of the study was to compare the tested parameters, taking into account procoagulant activity, assessed by the level of D-dimer.
The study showed that a high level of D-dimer (> 1 mg/l) in patients with COVID-19 is associated with a lower level of expression of the IFNA gene and an increase of the level of expression of pro-inflammatory cytokines genes TNF and IL1B compared with a subgroup with a low level of D-dimer (< 1 mg/l). In the subgroup with a low level of D-dimer, the expression of TNF and IL1B genes had no difference from the group of healthy persons.
Conclusion. An increase of the level of TLR7 gene expression combined with a decrease of IFNA expression in the group with a high level of D-dimer may indicate an imbalance in innate immunity factors. Elevated expression levels of the pro-inflammatory cytokines genes TNF and IL1B are associated with a high risk of thrombosis (as measured by D-dimer) and may be one of the markers of an unfavorable outcome of COVID-19.
Keywords:COVID-19; genes; ACE2; TLR7; innate immunity; proinflammatory cytokines; elderly patients
For citation: Grechenko V.V., Uvarova O.S., Gromova T.V., Artemyeva O.V., Gankovskaya L.V. Changes in the expression of genes encoding ACE2 and innate immunity molecules (TLR7, IFN-α, IL-1β, TNF) in elderly patients with COVID-19. Immunologiya. 2023; 44 (1): 72–82. DOI: https://doi.org/10.33029/0206-4952-2023-44-1-72-82 (in Russian)
Funding. The study had no sponsor support.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. The concept and design of the study – Gankovskaya L.V., collection and processing of the material – Uvarova O.S., statistical data processing – Grechenko V.V., writing the text – Grechenko V.V., Uvarova O.S., Gromova T. V., editing – Artemyeva O.V., Gankovskaya L.V., Grechenko V.V., approval of the final version of the article – Gankovskaya L.V., responsibility for the integrity of all parts of the article – Grechenko V.V.
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