Russian Journal of AllergyRussian Journal of Allergy1810-88302686-682XFarmarus Print Media141010.36691/RJA1410Research ArticleDynamics of basophil reactivity in the patients with allergic rhinitis on the background of allergen-specific immunotherapyBarychevaLiudmila Yu.<p>Head of the Department of Immunology<br />with a course of continuing professional education; allergist-immunologist, allergist-immunologist</p>for_ludmila@inbox.ruhttps://orcid.org/0000-0002-4069-0566DushinaLiudmila V<p>Assistant of the Department of Immunology with a course of continuing professional education; doctor-laboratory assistant of the Laboratory Diagnostics Department</p>dushina.stv@gmail.comGolubevaMarina V.<p>Head of the Department of Pediatric Infectious Diseases, MD, PhD,<br />Professor</p>mmvg@rambler.ruMinasyanMilana M.<p>Assistant of the Department of Immunology with a course of continuing professional education, Candidate of Medicine, MD</p>m.milana84@mail.ruhttps://orcid.org/0000-0002-5823-7479MedvedenkoYulia N.<p>Assistant of the Department of Immunology with a course of continuing professional education; allergist-immunologist</p>juliasun2008@yandex.ruhttps://orcid.org/0000-0001-8276-7894Stavropol State Medical UniversityStavropol Regional Clinical Consulting and Diagnostic Center2912202017475841012202015122020Copyright © 2021, Pharmarus Print Media2021<p><strong>BACKGROUND:</strong> Allergen-specific immunotherapy (ASIT) helps to reduce spontaneous and to induce basophil reactivity, which is one of the major mechanisms of its effectiveness. A number of studies, though, have not confirmed the informative value of the basophil activation test (BAT), in case of ASIT, with house dust mites, meadow grass pollen, and wasp venom. BAT outcomes are likely to be influenced by the properties of the sensitizing allergen, the duration of ASIT, and the BAT markers that are used.</p>
<p><strong>AIMS:</strong> To evaluate the basophils reactivity in the patients sensitized to weed pollen and treated with allergen-specific therapy.</p>
<p><strong>MATERIALS AND METHODS:</strong> The study involved 60 patients (aged 1655) with allergic rhinitis sensitized to weed pollen. The diagnosis was based on the skin test outcomes as well as on identifying specific antibodies to major allergens of ragweed, wormwood, timothy, and birch. The pre-seasonal ASIT involved water-salted extracts of pollen allergens during 2 years. Clinical symptoms and the immunotherapy effectiveness were evaluated 6 and 18 months after the ASIT started. BATs were made before the treatment, after the first and second courses of pre-seasonal ASIT, which corresponded to zero, the 3<sup>rd</sup> and the 15<sup>th</sup> months of the treatment. The activated basophils were identified based on the CRTH2<sup>pos</sup> CD203<sup>bright</sup>CD3<sup>neg</sup> phenotype.</p>
<p><strong>RESULTS:</strong> The first treatment course was completed by 52 patients, while the second one by 43 patients. A statistically significant decrease in spontaneous basophil reactivity was detected only after the second course of ASIT. The decrease in the allergen-induced basophil activation was identified in 67.4% of the samples obtained after the first ASIT course, and in 67.6% of samples taken after the second immunotherapy course. A decrease in the BAT stimulation index (BAT SI) was identified mainly in the patients featuring positive treatment outcomes.</p>
<p><strong>CONCLUSIONS:</strong> ASIT influences on the basophil reactivity indicators in the patients sensitized to weed pollen. The basophil activation test may be considered as a potential predictor of ASIT effectiveness.</p>allergic rhinitisallergen-specific immunotherapybasophil activation testаллергический риниталлергенспецифическая иммунотерапиятест активации базофилов[Pfaar O, Bonini S, Cardona V, Demoly P, Jakob T, Durham SR, et al. Perspectives in allergen immunotherapy: 2017 and beyond. Allergy. 2018;73 Suppl 104:5–23.doi: 10.1111/all.13355.][Lam HY, Tergaonkar V, Ahn KS. Mechanisms of allergen-specific immunotherapy for allergic rhinitis and food allergies. Biosci Rep. 2020;40(4):BSR20200256.doi: 10.1042/BSR20200256.][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.][Shamji MH, Durham SR. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers. J Allergy Clin Immunol. 2017;140(6):1485–1498.doi: 10.1016/j.jaci.2017.10.010.][Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens. World Allergy Organ J. 2015;8(1):1–12. doi: 10.1186/s40413-015-0063-2.][Khaitov RM, Il’ina NI, editors. Allergology and Clinical Immunology. Clinical guidelines. Moscow: GEOTAR-Media; 2019. 352 p. (In Russ).][Klimek L, Bachert C, Pfaar O, Becker S, Bieber T, Brehler R, et al. ARIA guideline 2019: treatment of allergic rhinitis in the German health system. Allergol Select. 2019;3(1):22–50. doi: 10.5414/ALX02120E.][Ado AD. Private allergology. Moscow: Meditsina; 1976. 510 p. (In Russ).][Feng M, Zeng X, Su Q, Shi X, Xian M, Qin R, Li J. Allergen immunotherapy-induced immunoglobulin G4 reduces basophil activation in house dust mite-allergic asthma patients. Front Cell Dev Biol. 2020;8:30. doi: 10.3389/fcell.2020.00030.][Hoffmann HJ, Santos AF, Mayorga C, Nopp A, Eberlein B, Ferrer M, et al. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease. Allergy. 2015;70(11):1393–405. doi: 10.1111/all.12698.][Kepil Özdemir S, Sin BA, Güloğlu D, İkincioğulları A, Gençtürk Z, Mısırlıgil Z. Short-term preseasonal immunotherapy: is early clinical efficacy related to the basophil response? Int Arch Allergy Immunol. 2014;164(3):237–245. doi: 10.1159/000365628.][Zidarn M, Košnik M, Silar M, Grahek A, Korosec P. Rhinitis symptoms caused by grass pollen are associated with elevated basophile allergen sensitivity and a larger grass-specific immunoglobulin E fraction. Clin Exp Allergy. 2012;42(1):49–57. doi: 10.1111/j.1365-2222.2011.03838.][Kim SH, Kim SH, Chung SJ, Kim JH, Lee SY, Kim BK, et al. Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis. Asia Pac Allergy. 2018;8(1):e6.doi: 10.5415/apallergy.2018.8.e6.][Czarnobilska EM, Bulanda M, Śpiewak R. The usefulness of the basophil activation test in monitoring specific immunotherapy with house dust mite allergens. Postepy Dermatol Allergol. 2018;35(1):93–98. doi: 10.5114/ada.2018.73169.][Van Overtvelt L, Baron-Bodo V, Horiot S, Moussu H, Ricarte C, Horak F, et al. Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy. Allergy. 2011;66(12):1530–1537.doi: 10.1111/j.1398-9995.2011.02696.x.][Erdmann SM, Sachs B, Kwiecien R, Moll-Slodowy S, Sauer I, Merk HF. The basophil activation test in wasp venom allergy: sensitivity, specificity and monitoring specific immunotherapy. Allergy. 2004;59(10):1102–1109.doi: 10.1111/j.1398-9995.2004.00624.x.][Witting Christensen SK, Kortekaas Krohn I, Thuraiaiyah J, Skjold T, Schmid JM, Hoffmann HJ. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK. Allergy. 2014;69(10):1343–1349.doi: 10.1111/all.12482.][Santos AF, Douiri A, Becares N, Wu SY, Stephens A, Radulovic S, et al. Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children. J Allergy Clin Immunol. 2014;134(3):645–652.doi: 10.1016/j.jaci.2014.04.039.][Imoto Y, Takabayashi T, Sakashita M, Tokunaga T, Ninomiya T, Ito Y, et al. Peripheral basophil reactivity, CD203c expression by Cryj1 stimulation, is useful for diagnosing seasonal allergic rhinitis by Japanese cedar pollen. Immun Inflamm Dis. 2015;3(3):300–308. doi: 10.1002/iid3.69.][Bidad K, Nawijn MC, Van Oosterhout AJ, Van der Heide S, Elberink JN. Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy. Cytometry B Clin Cytom. 2014;86(3):183–190. doi: 10.1002/cyto.b.21148.][Schmid JM, Würtzen PA, Dahl R, Hoffmann HJ. Early improvement in basophil sensitivity predicts symptom relief with grass pollen immunotherapy. J Allergy Clin Immunol. 2014;134(3):741–744.e5. doi: 10.1016/j.jaci.2014.04.029.][Caruso M, Cibella F, Emma R, Campagna D, Tringali G, Amaradio MD, et al. Basophil biomarkers as useful predictors for sublingual immunotherapy in allergic rhinitis. Int Immunopharmacol. 2018;60:50–58. doi: 10.1016/j.intimp.2018.04.034.][Tsai M, Mukai K, Sharon Chinthrajah R, Nadeau KC, Galli SJ. Sustained successful peanut oral immunotherapy associated with low basophil activation and peanut-specific IgE Lower basophil activation and peanut-specific IgE are associated with better outcomes after peanut oral immunotherapy. J Allergy Clin Immunol. 2020;145(3):885–896.doi: 10.1016/j.jaci.2019.10.038.][Patil SU, Steinbrecher J, Calatroni A, Smith N, Ma A, Ruiter B, et al. Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy. J Allergy Clin Immunol. 2019;144(5):1310–1319.doi: 10.1016/j.jaci.2019.07.028.]