Modern ideas about mechanisms of allergen-specific immunotherapy

Cover Page

Cite item

Full Text

Abstract

Reviews of domestic and foreign authors consider different approaches to understanding the formation of immunological and clinical tolerance induced by allergen-specific immunotherapy (ASIT). Despite the wide variety of theoretical research, the mechanism of the body’s immune system’s response to ASIT remains unclear.

The aim of this review is to analyze the current understanding of the mechanisms of formation of changes in the body’s reactivity in response to an allergen after ASIT. It is known that the type of response to the antigen is determined by its dose. In low-dose ASIT tolerance to the antigen is formed in the absence of inflammation, which is apparently associated with the activation of specific high-affinity receptors on cells of the immune system. High doses of allergen in ASIT probably lead to a rearrangement of cellular receptors, causing a decrease in their number by internalization or a weakening of their sensitivity to an excessive signal (desensitization). Due to a decrease in the number of receptors and / or their loss of sensitivity, the response to the antigen changes according to the principle of negative regulation, implemented at the level of receptor or postreceptor mechanisms. The formation of an anti-inflammatory cytokine response to antigen contributes to the differentiation of naive T cells into inducible regulatory T cells (iTreg). The suppressing effect of Treg on immune system cells affects Th effector cells, mast cells, basophils, eosinophils, B cells, and dendritic cells.

The occurring immunological shifts form a new type of tolerant response to the allergen, namely, the change in the type of immunoglobulins from IgE to IgG and IgA and new phenotypes of T memory and B memory cells.

About the authors

Stanislava Yu. Petrova

Mechnikov Research Institute of Vaccines and Sera

Author for correspondence.
Email: petrovastanislava@yandex.ru
ORCID iD: 0000-0003-3034-0148

Senior researcher of the Laboratory of Allergens, MD

Russian Federation, Moscow

Svetlana V. Khlgatian

Mechnikov Research Institute of Vaccines and Sera

Email: svetkh@gmail.com
ORCID iD: 0000-0001-8354-7682

Leading researcher of the Laboratory of Allergens, Doctor of Biological Sciences

Russian Federation, Moscow

Valentina М. Berzhets

Mechnikov Research Institute of Vaccines and Sera

Email: laball@yandex.ru
ORCID iD: 0000-0001-5055-7593

Head of the Laboratory of Allergens, professor

Russian Federation, Moscow

Nina S. Petrova

Mechnikov Research Institute of Vaccines and Sera

Email: s.levina2005@yandex.ru

Leading researcher of the Laboratory of Allergens, , Сandidate of Biological Sciences

Russian Federation, Moscow

Olga V. Radikova

Mechnikov Research Institute of Vaccines and Sera

Email: radikova@rambler.ru
ORCID iD: 0000-0001-9710-6968

Research fellow of the Laboratory of Allergens, MD

Russian Federation, Moscow

References

  1. Yarilin AA. Immunology. Мoscow: GEOTAR-Media; 2010. (In Russ.).
  2. Burmester GR, Pezzutto А. Visual immunology. Мoscow: Laboratoriya znaniy; 2018. (In Russ.).
  3. Yarilin. AA. Transkriptsionnyye regulyatory differentsirovki T-khelperov. Immunologiya. 2010;31(3):153–168. (In Russ.).
  4. Gushchin IS. IgE-mediated hypersensitivity as a response to barrier tissue disfunction. Immunologiya. 2015;36(1):45–52. (In Russ.).
  5. Petrova SYu, Khlgatian SV, Berzhets VM, Radikova OV. Modern concept of pathogenesis of atopic diseases. Immunopathology, allergology, infectology. 2019;(1):73–88. (In Russ.). doi: 10.14427/jipai.2019.1.72
  6. Petrova SYu, Berzhets VM, Petrova NS, et al. Future prospect of allergens’ medical forms. From abstract problems to concrete solutions. Immunopathology, allergology, infectology. 2018;(1):40–47. (In Russ.). doi: 10.14427/jipai.2018.1.40
  7. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J. 2015;8(1):17. doi: 10.1186/s40413-015-0063-2
  8. Jutel M, Akdis CA. Immunological mechanisms of allergen-specific immunotherapy. Allergy. 2011;66(6):725–732. doi: 10.1111/j.1398-9995.2011.02589.x
  9. Fujita Н, Soyka МВ, Akdis М, Akdis CA. Mechanisms of allergen-specific immunotherapy. Clin Transl Allergy. 2012;2(1):2. doi: 10.1186/2045-7022-2-2
  10. Jutel M, Agache I, Bonini S, et al. International consensus on allergen immunotherapy II: mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016;137(2):358–368. doi: 10.1016/j. jaci.2015.12.1300
  11. Pichuzhkina OV, Gushchin IS, Kurbacheva OM. Rearrangement of immune response as a result of allergen-specific immunotherapy. Immunologiya. 2013;(1):43–48. (In Russ.).
  12. Shamji MH, Durham SR. Mechanisms of immunotherapy to aeroallergens. Clin Exp Allergy. 2011;41(9):1235–1246.doi: 10.1111/j.1365-2222.2011.03804.x
  13. Vykhrystsenka LR. Mechanisms of oral tolerance to allergens. Immunopathology, allergology, infectology. 2015;4:16–26. (In Russ.). doi: 10.14427/jipai.2015.4.16
  14. Boonstra A, Asselin-Paturel C, Gilliet M, et al. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T-helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J Exp Med. 2003;197(1):101–109. doi: 10.1084/jem.20021908
  15. Orlov RS, Nozdrachev AD. Normal physiology. Мoscow: GEOTAR-Media; 2010. (In Russ.).
  16. Cleyrat C, Darehshouri A, Anderson KL, et al. The architectural relationship of components controlling mast cell endocytosis. J Cell Sci. 2013;126(Pt 21):4913–4925.doi: 10.1242/jcs.128876
  17. Muller UR, Jutel M, Reimers A, et al. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J Allergy Clin Immunol. 2008;122(5):1001–1007. doi: 10.1016/j.jaci.2008.08.007
  18. Kondo T, Kawai T, Akira S. Dissecting negative regulation of Toll-like receptor signaling. Trends Immunol. 2012;33(9):449–458. doi: 10.1016/j.it.2012.05.002
  19. Woo HY, Kim YS, Kang NI, et al. Mechanism for acute oral desensitization to antibiotics. Allergy. 2006;61(8):954–958. doi: 10.1111/j.1398-9995.2006.01147.x
  20. Kurbacheva OM, Polner SA, Smirnov DS. Allergic rhinitis. Perpetual problem and current solutions. Meditsinskiy sovet. 2015;(3):84–91. (In Russ.).doi: 10.21518/2079-701X-2015-3-84-91
  21. Branco A, Yoshikawa F, Pietrobon AJu, Sato MN. Role of Histamine in modulating the immune response and inflammation. Mediators Inflamm. 2018;2018:9524075.doi: 10.1155/2018/9524075
  22. O’Mahony L, Akdis M, Akdis CA. Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol. 2011;128(6):1153–1162.doi: 10.1016/j.jaci.2011.06.051
  23. Caron G, Delneste Y, Roelandts E, et al. Histamine induces CD86 expression and chemokine production by human immature dendritic cells. J Immunol. 2001;166(10):6000–6006. doi: 10.4049/jimmunol.166.10.6000
  24. Meiler F, Zumkehr J, Klunker S, et al. In vivo switch to IL-10-secreting T-regulatory cells in high dose allergen exposure. J Exp Med. 2008;205(12):2887–2898.doi: 10.1084/jem.20080193
  25. Jutel M, Żak-Nejmark T, Wrzyszcz M, Malolepszy J. Histamine receptor expression on peripheral blood CD4+ lymphocytes is influenced by ultra-rush bee venom immunotherapy. Allergy. 1997;52(37):88.
  26. Eberlein-Konig B, Ullmann S, Thomas P, Przybilla B. Tryptase and histamine release due to a sting challenge in bee venom allergic patients treated successfully or unsuccessfully with hyposensitization. Clin Exp Allergy. 1995;25(8):704–712.doi: 10.1111/j.1365-2222.1995.tb00007.x
  27. Plewako H, Wosinska K, Arvidsson M, et al. Basophil interleukin 4 and interleukin 13 production is suppressed during the early phase of rush immunotherapy. Int Arch Allergy Immunol. 2006;141(4):346–353. doi: 10.1159/000095461
  28. Sviridova VS, Klimov VV, Denisov AA, et al. immunoregulator subpopulations of T-cells in tumor growth and allergic diseases. Sibirskii onkologicheskii zhurnal. 2010;(3):38–47. (In Russ.).
  29. Jutel M, Agache I, Bonini S, et al. International consensus on allergen immunotherapy II. Allergy Clin Immunol. 2016;137(2):358–368. doi: 10.1016/j.jaci.2015.12.1300
  30. Van de Veen W, Stanic B, Yaman G, et al. IgG4 production is confined to human IL-10-producing regulatory B-cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131(4):1204–1212.doi: 10.1016 / j. jaci.2013.01.014
  31. Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol. 2007;119(4):780–791.doi: 10.1016/j.jaci.2007.01.022
  32. Calderon M, Casale T, Togias A, et al. Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to regulation and beyond. J Allergy Clin Immunol. 2011;127(1):30–38. doi: 10.1016/j. jaci.2010.08.024
  33. Meadows A, Kaambwa B, Novielli N, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Health Technol Assess. 2013;17(27):VI, XI–XIV, 1–322. doi: 10.3310/hta17270
  34. Patent RUS 2216353 C1. 2002. Berzhets VM, Коreneva ЕА, Petrova NS, Pishchulina LA. Sposob polucheniya granulirovannoi lekarstvennoi formy iz allergena kleshchei roda Dermatophagoides farinae. Available from: https://www.elibrary.ru/item.asp?id=37905642 (In Russ.).
  35. Berzhets VM, Khlgatyan SV, Petrova SYu, et al. Study of the properties of the mixed water-salt house dust mite allergen aiming to design its sublingual form. Meditsinskaya immunologya. 2018;20(4):597–600. (In Russ.).doi: 10.15789/1563-0625-2018-4-597-600
  36. Berzhets VM, Коreneva ЕА, Khlgatyan SV, et al. Study of the immunogenic properties of granulated form of the mixed-allergen from house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae. Immunopathology, allergology, infectology. 2019;2:66–71. (In Russ.). doi: 10.14427/jipai.2019.2.56
  37. Berzhets VM, Babakhin AA, Petrova NS, et al. New forms of home dust mite allergoid. Journal of microbiology epidemiology immunobiology. 2019;3:15–21. (In Russ.).doi: 10.36233/0372-9311-2019-3-15-21
  38. Makatsori M, Pfaar O, Lleonart R, Calderon MA. Recombinant allergen immunotherapy: clinical evidence of efficacy – a review. Curr Allergy Asthma Rep. 2013;13(4):371–380.doi: 10.1007/s11882-013-0359-7
  39. Valenta R, Linhart B, Swoboda I, Niederberger V. Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. Allergy. 2011;66(6):775–783.doi: 10.1111/j.1398-9995.2011.02565.x
  40. Marth K, Focke-Tejkl M, Lupinek Ch, et al. Allergen peptides, recombinant allergens and hypoallergens for allergen-specific immunotherapy. Curr Treat Options Allergy. 2014;1(1):91–106. doi: 10.1007/s40521-013-0006-5
  41. Eckl-Dorna J, Weber M, Stanek V, et al. Two years of treatment with the recombinant grass pollen allergy vaccine BM32 induces a continuously increasing allergen-specific IgG4 response. EBioMedicine. 2019;50:421–432.doi: 10.1016/j.ebiom.2019.11.006

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Figure: 1. ASIT mechanisms by Jutel et al., 2016 [10]; Akdis et al., 2015 [7]

Download (150KB)
Indexing metadata
3. Figure: 2. Formation of immunological tolerance in ASIT according to Shamji and Durham, 2011 [12]. Repeated exposure to allergens in atopic-prone patients results in IgE-mediated allergic reactions. ASIT with high doses of the allergen leads to the induction of Tregs [adaptive Tregs (aTreg) and natural Tregs (nTreg)] and cytokines such as IL-10 and TGF-â. The release of cytokines plays an important role in suppressing Th2 reactions and contributes to the synthesis of allergen-specific antibodies of the IgA1, IgA2 and IgG4 isotypes, which have inhibitory activity. The ongoing immunological changes contribute to the physiological alignment of the Th2 / Th1 ratio due to a shift in differentiation towards Th1. The suppressive effect of Treg on cells of the immune system affects not only effector Th, but also mast cells, basophils, eosinophils, B cells, dendritic cells

Download (401KB)
Indexing metadata

Copyright (c) 2021 Pharmarus Print Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies