Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press141010.36691/RJA1410Original study articlesОригинальные исследованияResearch ArticleDynamics of basophil reactivity in the patients with allergic rhinitis on the background of allergen-specific immunotherapyДинамика реактивности базофилов у пациентов с аллергическим ринитом на фоне аллергенспецифической иммунотерапииhttps://orcid.org/0000-0002-4069-05668946-3393BarychevaLiudmila Yu.БарычеваЛюдмила Юрьевна
Russian Federation

Head of the Department of Immunologywith a course of continuing professional education; allergist-immunologist, allergist-immunologist

зав. кафедрой иммунологии скурсом ДПО; врачаллерголог-иммунолог, д.м.н., профессор

for_ludmila@inbox.ru3599-5095DushinaLiudmila VДушинаЛюдмила Валентиновна
Russian Federation

Assistant of the Department of Immunology with a course of continuing professional education; doctor-laboratory assistant of the Laboratory Diagnostics Department

ассистент кафедры иммунологии с курсом ДПО; врач-лаборант отделения лабораторной диагностики

dushina.stv@gmail.com7193-5101GolubevaMarina V.ГолубеваМарина Викторовна
Russian Federation

Head of the Department of Pediatric Infectious Diseases, MD, PhD,Professor

зав. кафедрой детских инфекционных болезней, доктор медицинских наук, профессор

mmvg@rambler.ruhttps://orcid.org/0000-0002-5823-74798518-5443MinasyanMilana M.МинасянМилана Михайловна
Russian Federation

Assistant of the Department of Immunology with a course of continuing professional education, Candidate of Medicine, MD

доцент кафедры иммунологии с курсом ДПО, кандидат медицинских наук

m.milana84@mail.ruhttps://orcid.org/0000-0001-8276-78945602-6559MedvedenkoYulia N.МедведенкоЮлия Николаевна
Russian Federation

Assistant of the Department of Immunology with a course of continuing professional education; allergist-immunologist

ассистент кафедры иммунологии с курсом ДПО; врач аллерголог-иммунолог

juliasun2008@yandex.ruStavropol State Medical UniversityСтавропольский государственный медицинский университетStavropol Regional Clinical Consulting and Diagnostic CenterСтавропольский краевой клинический консультативно-диагностический центр2912202017475841012202015122020Copyright ©; 2021, Pharmarus Print MediaCopyright ©; 2021, Фармарус Принт Медиа2021Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/1410

BACKGROUND: 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.

AIMS: To evaluate the basophils reactivity in the patients sensitized to weed pollen and treated with allergen-specific therapy.

MATERIALS AND METHODS: The study involved 60 patients (aged 16–55) 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 3rd and the 15th months of the treatment. The activated basophils were identified based on the CRTH2pos CD203brightCD3neg phenotype.

RESULTS: 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.

CONCLUSIONS: 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.

ВВЕДЕНИЕ. Аллергенспецифическая иммунотерапия (АСИТ) способствует снижению спонтанной и индуцированной реактивности базофилов, что является одним из основных механизмов ее эффективности. Однако в ряде исследований не подтверждена информативность теста активации базофилов (Basophil activation test – BAT) при АСИТ аллергенами клеща домашней пыли, пыльцы луговых трав, яда осы. Вероятно, на результаты BAT оказывают влияние свойства сенсибилизирующего аллергена, используемые маркеры BAT и продолжительность АСИТ.

ЦЕЛЬ — оценить реактивность базофилов у пациентов, сенсибилизированных пыльцой сорных трав, получавших АСИТ.

МАТЕРИАЛЫ И МЕТОДЫ. Обследованы 60 пациентов с аллергическим ринитом, сенсибилизированных к пыльце сорных трав, в возрасте от 16 до 55 лет. При постановке диагноза использовали результаты проведения кожных проб и определения антител к мажорным аллергенам амброзии, полыни, тимофеевки, березы. Для предсезонной АСИТ применяли водно-солевые экстракты пыльцевых аллергенов в течение 2 лет. Оценку клинических симптомов и эффективности иммунотерапии проводили через 6 и 18 мес от начала АСИТ. Тесты активации базофилов выполняли до лечения, после первого и второго курсов предсезонной АСИТ, что соответствовало 0-, 3- и 15-му мес лечения. Активированные базофилы определяли по фенотипу CRTH2+ CD203brightCD3–.

РЕЗУЛЬТАТЫ. Первый курс лечения завершили 52 пациента, второй курс – 43. Статистически значимое уменьшение спонтанной реактивности базофилов установлено только после второго курса АСИТ. Снижение индуцированной аллергеном активации базофилов выявлено в 67,4% проб после первого курса АСИТ и в 67,6% проб – после второго. Снижение индекса стимуляции BAT (ИС BAT) установлено преимущественно у пациентов с положительными результатами лечения.

ЗАКЛЮЧЕНИЕ. АСИТ оказывает влияние на показатели реактивности базофилов у пациентов, сенсибилизированных к пыльце сорных трав. Высказано предположение, что показатель BAT может рассматриваться в качестве потенциального предиктора эффективности АСИТ.

allergic rhinitisallergen-specific immunotherapybasophil activation testаллергический риниталлергенспецифическая иммунотерапиятест активации базофиловPfaar 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.Pfaar O., Bonini S., Cardona V., Demoly P., Jakob T., Durham S.R., et al. Perspectives in allergen immunotherapy: 2017 and beyond // Allergy. 2018. Vol. 73. Suppl. 104. P. 5–23.doi: 10.1042/BSR20200256.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.Lam H.Y., Tergaonkar V., Ahn K.S. Mechanisms of allergen-specific immunotherapy for allergic rhinitis and food allergies // Biosci Rep. 2020. Vol. 40. N 4. P. 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.Van de Veen W., Wirz O.F., Globinska A., Akdis M. Novel mechanisms in immune tolerance to allergens during natural allergen exposure and allergen-specific immunotherapy // Curr Opin Immunol. 2017. Vol. 48. P. 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.Shamji M.H., Durham S.R. Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers // J Allergy Clin Immunol. 2017. Vol. 140. N 6. P. 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.Akdis C.A., Akdis M. Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens // World Allergy Organ J. 2015. Vol. 8. N 1. P. 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).Аллергология и клиническая иммунология. Клинические рекомендации / под ред. Р.М. Хаитова, Н.И. Ильиной. М. : ГЭОТАР-Медиа, 2019. 352 с.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.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. Vol. 3. N 1. P. 22–50. doi: 10.5414/ALX02120E.Ado AD. Private allergology. Moscow: Meditsina; 1976. 510 p. (In Russ).Адо А.Д. Частная аллергология. М. : Медицина, 1976. 510 c.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.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. Vol. 8. P. 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.Hoffmann H.J., Santos A.F., 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. Vol. 70. N 11. P. 1393–1405. 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.Kepil Özdemir S., Sin B.A., 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. Vol. 164. N 3. P. 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.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. Vol. 42. N 1. P. 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.Kim S.H., Kim S.H., Chung S.J., Kim J.H., Lee S.Y., Kim B.K., et al. Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis // Asia Pac Allergy. 2018. Vol 8. N 1. P. 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.Czarnobilska E.M., Bulanda M., Śpiewak R. The usefulness of the basophil activation test in monitoring specific immunotherapy with house dust mite allergens // Postepy Dermatol Allergol. 2018. Vol. 35. N 1. P. 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.Van Overtvelt L., Baron-Bodo V., Horiot S., Moussu H., Ricar- te C., Horak F., et al. Changes in basophil activation during grass-pollen sublingual immunotherapy do not correlate with clinical efficacy // Allergy. 2011. Vol. 66. N 12. P. 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.Erdmann S.M., Sachs B., Kwiecien R., Moll-Slodowy S., Sauer I., Merk H.F. The basophil activation test in wasp venom allergy: sensitivity, specificity and monitoring specific immunotherapy // Allergy. 2004. Vol. 59. N 10. P. 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.Witting Christensen S.K., Kortekaas Krohn I., Thuraiaiyah J., Skjold T., Schmid J.M., Hoffmann H.J. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK // Allergy. 2014. Vol. 69. N 10. P. 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.Santos A.F., Douiri A., Becares N., Wu S.Y., Stephens A., Radulovic S., et al. Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children // J Allergy Clin Immunol. 2014. Vol. 134. N 3. P. 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.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. Vol. 3. N 3. P. 300–308.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.Bidad K., Nawijn M.C., Van Oosterhout A.J., Van der Heide S., Elberink J.N. Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy // Cytometry B Clin Cytom. 2014. Vol. 86. N 3. P. 183–190.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.Schmid J.M., Würtzen P.A., Dahl R., Hoffmann H.J. Early improvement in basophil sensitivity predicts symptom relief with grass pollen immunotherapy // J Allergy Clin Immunol. 2014. Vol. 134. N 3. P. 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.Caruso M., Cibella F., Emma R., Campagna D., Tringali G., Amaradio M.D., et al. Basophil biomarkers as useful predictors for sublingual immunotherapy in allergic rhinitis // Int Immunopharmacol. 2018. Vol. 60. P. 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.Tsai M., Mukai K., Sharon Chinthrajah R., Nadeau K.C., Galli S.J. 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. Vol. 145. N 3. P. 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.Patil S.U., 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. Vol. 144. N 5. P. 1310–1319. doi: 10.1016/j.jaci.2019.07.028.