Expression of the TNFSF13B, APRIL, VEGF, FGF1 и EGF genes in different phenotypes of chronic rhinosinusitis with nasal polyps

Abstract

Background. Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic hyperplastic inflammatory process based on remodeling in the mucosa membrane of the paranasal sinuses leading to the formation of polyps. According to modern concepts, various growth factors can take part in the remodeling of the respiratory tract.

The aim – to study the level of growth factors genes expression in nasal polyps’ tissue in different phenotypes of CRSwNP.

Material and methods. 72 patients with bilateral CRSwNP were divided into 3 groups according to disease phenotype each of 24 patients: Group I – CRSwNP without asthma (BA) and allergy; Group II – CRSwNP with allergic BA; Group III – CRSwNP with nonallergic BA. Comparison group – patients with hypertrophic rhinitis without BA and atopy. We used real-time polymerase chain reaction in polyp’ tissue to study the levels of genes expression encoding proteins EGF, VEGF, FGF, BAFF and APRIL.

Results. The expression of genes TNFSF13B и FGF1 (encoding factors BAFF and FGF) in all CRSwNP phenotypes was statistically significantly higher than in the comparison group. Among the phenotypes of CRSwNP these growth factors were significantly lower in patient with CRSwNP and allergic BA. The expression of VEGF and APRIL in nasal polyps in all groups was lower than in the comparison group without statistically significantly. The expression of the gene encoding EGF was detected only in the comparison group, whereas the expression of this gene was not detected in the polyps’ tissue.

Conclusion. We demonstrated an increase of TNFSF13B и FGF1 genes in polypous tissue in all CRSwNP phenotypes, while the expression of EGF, VEGF and APRIL genes in comparison group was significantly lower or wasn’t detected. These data indicate the involvement of BAFF and FGF in the formation and growth of polyps. BAFF in the polypous tissue promotes the maturation of B-lymphocytes and their production of immunoglobulins. As the same time, FGF induces tissue fibrosis. High expression level of TNFSF13B and FGF1 genes suggest that their protein products – BAFF and FGF – can be considered as predictive biomarkers of the formation and recurrence of nasal mucosal polyps and paranasal sinus polyps, especially in the absence of atopy.

It is worth noting separately that all the patients with CRSwNP have the lowest expression of EGF gene detected in the polyp tissue. Therefore, the participation of EGF in polyp formation seems unlikely. Perhaps there isn’t the epithelial damage in the processes. VEGF and APRIL are responsible for hypertrophy of the nasal mucosa and paranasal sinuses, but do not cause polyp formation, regardless of the presence of atopy. This indicates that the molecular mechanisms of CRSwNP associated with allergic BA have their own characteristics that require additional research.

Keywords:chronic rhinosinusitis with nasal polyps; phenotypes, mucosal remodeling; B cell activating factor (BAFF); proliferation-inducing ligand (APRIL); vascular endothelial growth factor (VEGF); fibroblast growth factor (FGF); epidermal growth factor (EGF); genes

For citation: Kurbacheva O.M., Savlevich E.L., Egorov V.I., Dyneva M.E., Shilovskiy I.P., Kovchina V.I., Nikolskii A.A., Barvinskaia E.D., Kaganova M.M., Mitrofanova Е.S., Savushkina E.Y., Gaganov L.E., Khaitov M.R. Expression of the TNFSF13B, APRIL, VEGF, FGF1и EGF genes in different phenotypes of chronic rhinosinusitis with nasal polyps. Immunologiya. 2022; 43 (5): 571–82. DOI: https://doi.org/10.33029/0206-4952-2022-43-5-571-582 (in Russian)

Funding. The study was supported by the grant of Russian Science Foundation No. 19-15-00272, https://rscf.ru/project/19-15-00272/.

Conflict of interests. The authors declare no conflict of interests.

Author’s contribution. Authors made an equal contribution to the writing the article.

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