Evaluation of the impact of genetically engineered biological therapy on HLA-E expression in bronchial asthma and atopic dermatitis
- 作者: Borisevich V.I.1, Boeva O.S.2, Abbasova V.S.1, Demina D.V.2, Kozlov V.A.2
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隶属关系:
- Novosibirsk State Medical University
- Research Institute of Fundamental and Clinical Immunology
- 期: 卷 28, 编号 4 (2025)
- 页面: 1067-1072
- 栏目: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/333272
- DOI: https://doi.org/10.46235/1028-7221-17263-EOT
- ID: 333272
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Globally, the prevalence of bronchial asthma (BA) alone reaches 19%, with the number of affected individuals showing an upward trend. Atopic dermatitis (AD) affects 25-30% of children and 7-10% of adults. Remission remains elusive even with advanced genetically engineered biological therapies. Consequently, research into immunopathogenic pathways and the development of novel therapeutic strategies remain critical. A typical representative of “non-classical” HLAs, the HLA-E molecule, is a perspective for study. These molecules are also expressed across various tissues, notably in the respiratory system (bronchial epithelium) and skin keratinocytes. As a cell surface protein, HLA-E participates in diverse immune response pathways. VL9 peptides stabilize HLA-E expression, enabling presentation to its primary receptors, NKG2, on natural killer (NK) cells. In adaptive immunity, HLA-E serves as a ligand for CD8+ cytotoxic T cell receptors (TCRs). This study aimed to evaluate HLA-E-bearing cells (CD4+, CD8+, CD14+) in patients with BA and AD, both before and 12 months after initiating genetically engineered biological therapy (GEBT). Peripheral blood mononuclear cells (PBMCs) were analyzed from healthy donors (n = 16), BA patients (n = 4), and AD patients (n = 5). AD patients received dupilumab (300 mg loading dose), while BA patients were treated with benralizumab (30 mg). Prior to therapy, both AD and BA patients exhibited lower proportions of HLA-E-positive CD4+ and CD8+T cells compared to healthy donors. No significant differences were observed in HLA-E expression on CD14+ monocytes. During treatment, HLA-E levels across all cell types in patients reached levels comparable to those in healthy donors. These findings suggest HLA-E’s involvement in disease pathogenesis and the modulating effects of GEBT on HLA-E-positive cell populations.
作者简介
Vadim Borisevich
Novosibirsk State Medical University
编辑信件的主要联系方式.
Email: borvad2001@mail.ru
Student
俄罗斯联邦, NovosibirskO. Boeva
Research Institute of Fundamental and Clinical Immunology
Email: starchenkova97@gmail.com
Resident, Postgraduate Student, Laboratory Research Assistant, Laboratory of Clinical Immunopathology
俄罗斯联邦, NovosibirskV. Abbasova
Novosibirsk State Medical University
Email: starchenkova97@gmail.com
Student
俄罗斯联邦, NovosibirskD. Demina
Research Institute of Fundamental and Clinical Immunology
Email: immunology@mail.ru
PhD (Medicine), Allergologist, Head, Department of Allergology
俄罗斯联邦, NovosibirskV. Kozlov
Research Institute of Fundamental and Clinical Immunology
Email: vakoz40@yandex.ru
PhD, MD (Medicine), Prosfessor, Full Member, Russian Academy of Sciences, Head, Laboratory of Clinical Immunopathology, scientific director
俄罗斯联邦, Novosibirsk参考
- Свист П.Г., Торчинский Н.В., Брико Н.И., Авдеев С.Н. Распространенность бронхиальной астмы и ХОБЛ в коморбидности с COVID-19 // Эпидемиология и вакцинопрофилактика, 2024. Т. 23, № 1. С. 66-76. [Svist P.G., Torchinsky N.V., Briko N.I., Avdeev S.N. Prevalence of bronchial asthma and COPD in comorbidity with COVID-19. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccinal Prevention, 2024, Vol. 23, no. 1, pp. 66-76. (In Russ.)]
- Потекаев Н.Н., Терещенко Г.П., Ханферьян Р.А., Савастенко А.Л. Иммунные механизмы атопического дерматита и новые подходы к таргетной биологической терапии // Медицинский совет, 2022. Т. 16, № 3, С. 130-136. [Potekaev N.N., Tereshchenko G.P., Khanferyan R.A., Savastenko A.L. Immune mechanisms of atopic dermatitis and new approaches to targeted biological therapy. Meditsinskiy sovet = Medical Council, 2022, Vol. 16, no. 3, pp. 130-136. (In Russ.)]
- Coupel S., Moreau A., Hamidou M., Horejsi V., Soulillou J.P., Charreau B. Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation. Blood, 2007, Vol. 109, no. 7, pp. 2806-2814.
- Cross-Najafi A.A., Farag K., Isidan A., Li W., Zhang W., Lin Z., Walsh J.R., Lopez K., Park Y., Higgins N.G., Cooper D.K.C., Ekser B., Li P. Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells attenuates human NK cell-mediated degranulation. Front. Immunol., 2023, Vol. 14, 1217809. doi: 10.3389/fimmu.2023.1217809.
- Fesneau O., Samson K.A., Rosales W., Jones B., Moudgil T., Fox B.A., Rajamanickam V., Duhen T. IL-12 drives the expression of the inhibitory receptor NKG2A on human tumor-reactive CD8 T cells. Nat. Commun., 2024, Vol. 15, no. 1, 9988. doi: 10.1038/s41467-024-54420-w.
- Franciosi J.R., Gelmini G.F., Roxo V.S., de Carvalho N.S., Bicalho M.D.G. Is there a role played by HLA-E, if any, in HPV immune evasion? Scand. J. Immunol., 2020, Vol. 91, no. 3, e12850. doi: 10.1111/sji.12850.
- Gillespie G.M., Quastel M.N., McMichael A.J. HLA-E: Immune receptor functional mechanisms revealed by structural studies. Immunol. Rev., 2025, Vol. 329, no. 1, e13434. doi: 10.1111/imr.13434.
- Joosten S.A., Sullivan L.C., Ottenhoff T.H. Characteristics of HLA-E restricted T-cell responses and their role in infectious diseases. J. Immunol. Res., 2016, Vol. 2016, 2695396. doi: 10.1155/2016/2695396.
- Kanevskiy L., Erokhina S., Kobyzeva P., Streltsova M., Sapozhnikov A., Kovalenko E. Dimorphism of HLA-E and its disease association. Int. J. Mol. Sci., 2019, Vol. 20, no. 21, 5496. doi: 10.3390/ijms20215496.
- Kraemer T., Celik A.A., Huyton T., Kunze-Schumacher H., Blasczyk R., Bade-Döding C. HLA-E: Presentation of a broader peptide repertoire impacts the cellular immune response-implications on HSCT outcome. Stem Cells Int., 2015, Vol. 2015, 346714. doi: 10.1155/2015/346714.
- Negrini S., Contini P., Murdaca G., Puppo F. HLA-G in Allergy: Does it play an immunoregulatory role? Front. Immunol., 2022, Vol. 12, 789684. doi: 10.3389/fimmu.2021.789684.
- Sauter J., Putke K., Schefzyk D., Pruschke J., Solloch U.V., Bernas S.N., Massalski C., Daniel K., Klussmeier A., Hofmann JA., Lange V., Schmidt A.H. HLA-E typing of more than 2.5 million potential hematopoietic stem cell donors: Methods and population-specific allele frequencies. Hum. Immunol., 2021, Vol. 82, no. 7, pp. 541-547.
- Simpson E.L. Comorbidity in atopic dermatitis. Curr. Dermatol. Rep., 2012, Vol. 1, no. 1, pp. 29-38.
- Toni Ho G.-G., Heinen F., Stieglitz F., Blasczyk R., Bade-Döding C. Dynamic interaction between immune escape mechanism and HLA-Ib regulation. In: Rezaei N. (ed.). Immunogenetics. IntechOpen, 2019. Available at: http://dx.doi.org/10.5772/intechopen.80731.
- White S.R., Nicodemus-Johnson J., Laxman B., Denner D.R., Naureckas E.T., Hogarth D.K., Stern R., Minc A., Solway J., Sperling A., Ober C. Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma. J. Allergy Clin. Immunol., 2017, Vol. 140, no. 3, pp. 857-860.
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