A comparison of different methods of the allergen-specific immunotherapy in patients with pollinosis: the results of open randomized study


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Abstract

Background. Allergen-specific immunotherapy (ASIT) is viewed as the only treatment that influences all patho-genetically significant parts of the allergic process in the initial and late phases of the IgE-mediated allergic reaction and modifies the abnormal immune reactivity to a specific allergen. Currently, sublingual (SLIT) and subcutaneous (SCIT) immunotherapy are most commonly used in clinical practice. Despite long experience of sublingual and subcutaneous immunotherapy application, questions remain about the preferred ASIT method and comparative effectiveness of different ASIT methods. This article evaluates the efficacy, benefits of SCIT and SLIT and highlights new findings related mechanisms and potential biomarkers. The aim of the study. To evaluate the comparative efficacy of different methods of ASIT (subcutaneous and sublingual) based on clinical data and biomarkers in the blood serum and other biological fluids in adult patients with allergic rhinoconjunctivitis (with/without asthma). Materials and methods. 60 patients with allergic rhinoconjunctivitis (with/without asthma) aged 18 to 50 were randomly assigned to 3 groups treated by sublingual immunotherapy with extracts of allergens, subcutaneous immunotherapy with extracts of allergens and subcutaneous with modified allergens (allergoids) respectively. Results. The efficiency of the first course of preseason ASIT (SCIT and SLIT) with extracts of allergens and aller-goids in the control of symptoms of allergic rhinoconjunctivitis (with/without asthma) was demonstrated. After the end of the first year pre-season ASIT data analysis scales (Total Symptom Score -TSS, Medircation Score -MS) revealed the best performance in the group of patients receiving SCIT with allergoids compared with patients receiving the SLIT with extracts of allergens: the scales of the TSS (p=0.023), MS (p=0.002). In addition, at the end of the maintenance phase of ASIT in patients treated with SCIT with allergoids the level of eosinophilic cationic protein (ECP) in the nasal lavage decreased by 22% (p=0.012), secretory immunoglobulin A (sIgA) in the nasal lavage increased by 70% (p=0.001), interleukin-10 (IL-10) in serum increased by 126% (p=0.006), allergen-specific IgG4 increased by 42% (p=0.01) from the initial values, that correlates with a decrease in the severity of clinical manifestations. In pollen season ECP level in nasal lavage was significantly (p=0.007) lower in a group of patients who received SCIT with allergoids compared with patients who received the SLIT with extracts of allergens. The most significant changes of serum level of IL-10 in the pollen season occurred in a group of patients receiving SCIT with allergoids compared with patients who received SLIT (p=0.013) and SCIT (p=0.001) with extracts of allergens. Conclusion. The study results deepen the existing understanding of the mechanisms of SCIT and SLIT. They allow to develop a comprehensive assessment of the therapy efficacy scheme based on clinical parameters and on monitoring of local (ECP, sIgA) and systemic biomarkers (IL-10, allergen-specific IgG4) as well.

About the authors

A Y Nasunova

LLC clinic «Seagull»

Email: aysulia@mail.ru
врач аллерголог-иммунолог

N M Nenasheva

Russian State Academy of Continued Medical Education, Healthcare Ministry of Russia

профессор кафедры клинической аллергологии

References

  1. Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;177:1572-1573. doi: 10.1016/s0140-6736(00)78276-6.
  2. Bousquet J, Pfaar O, Togias A. Schunemann HJ, Ansotegui I, Papadopoulos NG et al. 2019 ARIA Care pathways for allergen immunotherapy. Allergy. 2019. doi: 10.1111/all.13805.
  3. Global Initiative for Asthma - GINA. Pocket guide for asthma management and prevention. Update 2019. Available from: http://www.ginasthma.org/.
  4. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556-568. DOI: 10.1016/j. jaci.2015.04.047.
  5. Pitsios C, Demoly P, Bilo MB, Gerth van Wijk R, Pfaar O, Sturm GJ et al. Clinical contraindications to allergen immunotherapy: an EAACI position paper. Allergy. 2015;70:897-909. doi: 10.1111/all.12638.
  6. Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology (European Academy of Allergy and Clinical Immunology) PRACTALL consensus report. J Allergy Clin Immunol. 2013;131:1288-1296.e3. doi: 10.1016/jjaci.2013.01.049.
  7. Berings M, Karaaslan C, Altunbulakli C, Gevaert P, Akdis M, Bachert C et al. Advances and highlights in allergen immunotherapy: on the way to sustained clinical and immunologic tolerance. J Allergy Clin Immunol. 2017;140:1250-1267. doi: 10.1016/j.jaci.2017.08.025.
  8. Shamji MH, Durham SR. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol. 2017;140:1485-1498. DOI: 10.1016/j. jaci.2017.10.010.
  9. Van de Veen W, Wirz OF, Globinska A, Akdis M. Novel mechanisms in immune tolerance to allergens during natural allergen exposure and allergen-specific immunotherapy. Curr Opin Immunol. 2017;48:74-81. doi: 10.1016/j.coi.2017.08.012.
  10. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J. 2015;8:17. doi: 10.1186/s40413-015-0063-2.
  11. Kappen JH, Durham SR, Veen Hi, Shamji MH. Applications and mechanisms of immunotherapy in allergic rhinitis and asthma. Ther Adv Respir Dis. 2017;11:73-86. doi: 10.1177/1753465816669662.
  12. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W et al. International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016;137:358-368. DOI: 10.1016/j. jaci.2015.12.1300.
  13. Halken S, Larenas-Linnemann D, Roberts G, Calderon MA, Angier E, Pfaar O et al. EAACI guidelines on allergen immunotherapy: prevention of allergy. Pediatr Allergy Immunol. 2017;28:728-745. doi: 10.1111/pai.12807.
  14. Shamji MH, Kappen JH, Akdis M, Jensen-Jarolim E, Knol EF, Kleine-Tebbe J et al. Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunc-tivitis and allergic asthma: an EAACI Position Paper. Allergy 2017;72:1156-1173. doi: 10.1111/all.13138.
  15. Rossen RD, Butler WT, Gate tR, Szwed CF, Couch RB. Protein composition of nasal secretion during respiratory virus infection. Exp Biol Med. 1965;119:1169-1176. doi: 10.3181/00379727-119-30406.
  16. Гущин ИС, Курбачева ОМ. Аллергия и аллергенспецифи-ческая иммунотерапия. М.: Фармарус Принт Медиа. 2010 [Gushchin IS, Kurbacheva OM. Allergiya i allergenspecifcheska-ya immunoterapiya. M.: Farmarus Print Media. 2010 (In Russ.)].
  17. Sensi LG, Marccuci F, Migali E, Coniglio G. Eosinophil cationic protein and specific IgE in serum and nasal mucosa of patients with grass-pollen-allergic rhinitis and asthma. Allergy. 2001;56:231-236. doi: 10.1034/j.1398-9995.2001.056003231.x.
  18. Ohashi Y Nakai Y, Kakinoki Y, Ohno Y, Okamoto H, Sakamoto H et al. The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis. Clin Otolaryngol Allied Sci. 1997;22:100-105. doi: 10.1046/j.1365-2273.1997.00861.x.
  19. Bousquet J, Marsch H, Martinot B, Hejjaoui A, Wahl R, Michel FB. Doubleblind placebo-controlled immunotherapy with mixed grass-pollen allergoids. II. Comparison between parameters assessing the efficacy of immunotherapy. J Allergy Clin Immunol. 1988;82:439-446. doi: 10.1016/0091-6749(88)90017-6.
  20. Cosmi L, Santarlasci V, Angeli R, Liotta F, Maggi L, Frosali F et al. Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma- and interleukin-10-production. Clin Exp Allergy. 2006;36:261-272. doi: 10.1111/j.1365-2222.2006.02429.x.
  21. Norman P, Lichtenshtein L, Kageysobotka A, Marsh D. Controlled evaluation of allergoid in the immunotherapy of ragweed hay fever. J Allergy Clin Immunol. 1982;70;248-260. doi: 10.1016/0091-6749(82)90061-6.
  22. Kouser L, Kappen J, Walton RP, Shamji MH. Update on biomarkers to monitor clinical efficacy response during and post treatment in allergen immunotherapy. Curr Treat Options Allergy. 2017;4:43-53. doi: 10.1007/s40521-017-0117-5.
  23. Durham SR, Nelson HS, Nolte H, Bernstein DI, Creticos PS, Li Z et al. Magnitude of efficacy measurements in grass allergy immunotherapy trials is highly dependent on pollen exposure. Allergy. 2014;69:617-623. doi: 10.1111/all.12373.
  24. Rosner-Friese K, Kaul S, Vieths S, Pfaar O. Environmental exposure chambers in allergen immunotherapy trials: Current status and clinical validation needs. J Allergy Clin Immunol. 2015;135;636-643. doi: 10.1016/j.jaci.2014.10.045.

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