Aim. To evaluate the activity of the 4-1BB/4-1BBL signaling pathway in patients with influenza A (H1N1) virus-associated pneumonia.Materials and Methods. Here we enrolled 85 patients (41 males and 44 females, median age 48 (36-62) years) with influenza A (H1N1) virus-associated pneumonia. Among the exclusion criteria were unstable hemodynamics, BMI > 30, diabetes mellitus, HIV, tuberculosis, and cancer. Control group consisted of 15 healthy donors. The diagnosis of influenza A / H1N1 was confirmed by a positive PCR test. Pneumonia was diagnosed according to the Federal Clinical Guidelines «Community-acquired pneumonia in adults». Severity of pneumonia was evaluated by using CURB-65 and SMART-COP scales as well as IDSA/ATS criteria. Plasma concentration of 4-1BB (CD137 or TNFRSF9, an inducible costimulatory receptor expressed on activated T cells and antigen-presenting cells) was determined by flow cytometry.Results. Patients with moderate and severe influenza A (H1N1) virus-associated pneumonia had 1.5- and 2.4 fold-increased concentration of plasma 4-1ВВ as compared with the healthy controls.Conclusion. The 4-1BB/4-1BBL signaling pathway, involved in multiple immune reactions, is associated with the severity of influenza A (H1N1) virus-associated pneumonia.
The aim of the study. To identify the frequency of occurrence of TLR4 Asp299Gly (rs4986790) gene polymorphism and to establish its contribution to the development of organ dysfunction in patients with severe pneumonia associated with A/H1N1 influenza.Materials and methods. The study included 55 patients with severe pneumonia associated with A/H1N1 influenza. Inclusion criteria: severe pneumonia; consolidation/ground-glass syndrome according to chest X-ray/CT. Exclusion criteria: unstable hemodynamics; body mass index > 30; diabetes mellitus; HIV; tuberculosis, oncopathology. Verification of the pathogen in the respiratory swab was carried out using PCR method: A/H1N1 influenza virus RNA was identified. The age of the patients was 47 [38; 62] years. Among all the patients the proportion of men was 47.8 %, of women – 52.2 %. Patients were divided into 2 groups: group 1 included patients with SOFA scale (Sequential Organ Failure Assessment) score ≥ 2 points; group 2 – patients with SOFA scale score ˂ 2 points. Gene SNPs were determined by PCR method using standard kits developed by Research and Production Company “Litekh” (Moscow). Amplification of the TLR4 gene fragments was carried out in a thermocycler Bis-M111 (Bis-N LLC, Novosibirsk). Genomic DNA isolated from whole blood leukocytes using the “DNA Express Blood” reagent was analyzed followed by an amplification reaction. The amplification product was detected in a 3% agarose gel.Results. Multiple organ dysfunction (SOFA scale score ≥ 2 points) in patients with severe pneumonia associated with A/H1N1 influenza was registered in 24 (43.6 %) cases. When analyzing the frequency of occurrence of the minor Gly allele, according to genetic models, the differences were established between patients of the groups 1 and 2 in codominant (p = 0.023; odds ratio (OR) – 8.82 (0.95–81.89)) and dominant (p = 0.005; OR = 12.35 (1.40–109.07)) models.Conclusion. Severe pneumonia associated with A/H1N1 influenza is accompanied by a high incidence of organ dysfunction. The risk of organ failure development is 2.1 times increased in patients with severe pneumonia with identified TLR4 Asp299Gly gene polymorphism, which probably requires further study.
Aim of study. To evaluate the role of the CD27/CD70 signalling pathway in development of systemic inflammatory response in patients with pneumonia associated with influenza A (H1N1). Material and methods. A total of 85 patients with pneumonia associated with influenza A (H1N1) were examined. Among them, 30 patients had severe pneumonia and 55 patients had non-severe pneumonia. The patients’ age was 48±15 years. Men accounted for 47.8% and women 52.2% of the sample. The exclusion criteria were: unstable haemodynamics, BMI>30, diabetes mellitus, HIV, tuberculosis, oncopathology. The control group was constituted by 15 healthy donors. The diagnosis of influenza A (H1N1) was confirmed by a positive PCR test. The CURB / CRB-65 scales were used to diagnose and assess the severity of pneumonia; SMART-COP as well as the Federal Clinical Guidelines of the Ministry of Health of the Russian Federation «Community-acquired pneumonia in adults» 2019 and the IDSA / ATS criteria (in the presence of one «major» or three «minor» criteria, the pneumonia was regarded as «severe»). The plasma level of CD27 was evaluated via flow cytometry using the Beckman Coulter analyser (USA) using the LEGENDplex™ HU Immune Checkpoint Panel 1 Beckman Coulter (USA) kit for multiplex analysis. Results. It has been established that the plasma level of CD27 increased 1.8-fold in patients with severe pneumonia and underlying influenza A (H1N1) and 1.5-fold in patients with non-severe pneumonia compared to the control group, which is associated with the severity of the condition and the mortality rate. Conclusion. The CD27/CD70 signalling pathway is actively involved in the cascade of innate and adaptive immunity reactions in patients with pneumonia associated with influenza A (H1N1). CD27 activity is associated with the severity of the disease and the increase in mortality
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