Allergen chip in molecular diagnostic: from cohort analysis to personalized patient care

Background. The allergic diseases are growing everywhere. The exact diagnosis of allergens becomes more and more critical because it significantly affects the further treatment of the patient, including the question about using the allergen-specific immunotherapy. There are several laboratory and instrumental allergic tests among which the skin tests are the most available. Despite its low cost, this method is characterized by a large percentage of false-positive and, more importantly, false-negative results. In addition, the allergens that can be detected by skin tests are limited.

Aim. To conduct a comparative analysis of the effectiveness and diagnostic accuracy of allergen chips from different manufacturers and to evaluate their applicability in the molecular diagnosis of allergic diseases.

Results. ImmunoCAP ISAC and Allergy Explorer (ALEX) tests are gradually occupying their niche in the molecular diagnosis of allergic diseases. Both methods have their benefits and disadvantages. The high cost and difficulties in supplying foreign materials sharply limit the widespread use of allergy profiles in Russia. On the other hand, personalized medicine requires doctors to have a patient-centered care, which is completed using existing diagnostic tools. The allergy panels for various regions of Russia can solve this problem. Identifying the most common clinically significant molecules in each region will enable more accurate diagnosis of allergies and personalized patient treatment. This will improve medical care quality and increase therapy effectiveness.

Conclusion. Developing and implementing new diagnostic methods and creating allergen panels optimal for each region are important steps towards improving the diagnosis and treatment of allergic diseases. These measures will help clinicians more accurately identify relevant allergens and develop individual treatment plans for each patient, ultimately leading to better public health and lower economic costs for treating allergies.

1. Gushchin I.S. Allergy – late product of the immune system evolution. Immunologiya = Immunology 2019;40(2):43–57. (In Russ.). DOI: 10.24411/0206-4952-2019-12007.]

2. Ruby P., Holgate S.T., Canonica G.W. et al. WAO white book on allergy. World Allergy Organization, 2013. 242 р.

3. van de Veen W., Akdis M. Mechanisms of immune regulation in allergy. EAACI Global Atlas of Allergy 2014:90–1. DOI:10.1111/imr.12555

4. Tulaeva I., Kratzer B., Campana R. et al. Preventive allergenspecific vaccination against allergy: mission possible? Front Immunol 2020;11:1368. DOI: 10.3389/fimmu.2020.01368

5. Timoshenko D.O., Kofiadi I.A., Gudima G.O. et al. Epigenetics of bronchial asthma. Immunologiya = Immunology 2021;42(2):93–101. (In Russ.). DOI: 10.33029/0206-4952-2021-42-2-93-101

6. Seité S., Taieb C., Lazic Strugar T. et al. Self-reported allergies in Russia and impact on skin. SAGE Open Med 2020;8:2050312120957916. DOI: 10.1177/2050312120957916

7. Gushchin I.S. Doubts and hopes of allergology. Immunologiya = Immunology 2023;44(4):471–80. (In Russ.). DOI: 10.33029/0206-4952-2023-44-4-471-480

8. Federal clinical guidelines for the diagnosis of allergic diseases. 2015. Russian Association of Allergists and Clinical Immunologists (RAACI). (In Russ.). URL: https://raaci.ru/dat/pdf/klinicheskie_rekomendacii_po_diagnostike_az.pdf.

9. Ansotegui I.J., Melioli G., Canonica G.W. et al. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. World Allergy Organ J. 2020;13(2):100080. DOI: 10.1016/j.waojou.2019.100080

10. Khokha R.N. Diagnostics of allergies: realities and prospects. Part 1. Journal of the Grodno State Medical University 2020;18(3):329–34. DOI:10.25298/2221-8785-2020-18-3-329-334

11. Balabolkin I.I., Macharadze D.Sh. Skin tests: indications and contraindications. Voprosy sovremennoy pediatrii = Current Pediatrics 2013;12(3):31–7 (In Russ.). DOI: 10.15690/vsp.v12i3.678

12. Huang H.J., Campana R., Akinfenwa O. et al. Microarray-based allergy diagnosis: quo vadis? Front Immunol 2021;11:594978. DOI: 10.3389/fimmu.2020.594978

13. Brunetto B., Tinghino R., Braschi M.C. et al. Characterization and comparison of commercially available mite extracts for in vivo diagnosis. Allergy 2010;65(2):184–90. DOI: 10.1111/j.1398-9995.2009.02150.x

14. Elisyutina O.G., Shershakova N.N., Smirnov V.V. et al. New approaches to allergenspecifi c immunotherapy (ASIT): development of a recombinant vaccine against birch pollen allergy. Immunologiya = Immunology 2022;43(6):621–31. (In Russ.). DOI: 10.33029/0206-4952-2022-42-6-621-631

15. Kovaleva E.V., Rybalkin S.P., Shangaraeva V.A. et al. Study of reproductive toxicity of the recombinant allergy vaccine for the treatment of allergy to birch pollen and cross-related allergens. Immunologiya = Immunology 2023;44(6):721–30. (In Russ.). DOI: 10.33029/0206-4952-2023-44-6-721-730

16. Dramburg S., Hilger C., Santos A.F. et al. EAACI molecular allergology user's guide 2.0. Pediatr Allergy Immunol 2023;34 Suppl. 28:e13854. DOI: 10.1111/pai.13854

17. Skrindo I., Lupinek C., Valenta R. et al. The use of the MeDALL-chip to assess IgE sensitization: a new diagnostic tool for allergic disease? Pediatr Allergy Immunol 2015;26(3):239–46. DOI: 10.1111/pai.12366

18. Hiller R., Laffer S., Harwanegg C. et al. Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002;16(3):414–6. DOI: 10.1096/fj.01-0711fje

19. Lupinek C., Wollmann E., Baar A. et al. Advances in allergenmicroarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods 2014;66(1):106–19. DOI: 10.1016/j.ymeth.2013.10.008

20. Hamilton R. Microarray technology applied to human allergic disease. Microarrays (Basel) 2017;6(1):3. DOI: 10.3390/microarrays6010003

21. Canonica G.W., Ansotegui I.J., Pawankar R. et al. A WAO – ARIA – GA²LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J 2013;6(1):17. DOI: 10.1186/1939-4551-6-17

22. Matricardi P.M., Kleine-Tebbe J., Hoffmann H.J. et al. EAACI molecular allergology user's guide. Pediatr Allergy Immunol 2016;27(Suppl. 23):1–250. DOI: 10.1111/pai.12563

23. Wide L., Bennich H., Johansson S.G.O. Diagnosis of allergy by an in-vitro test for allergen antibodies. Lancet 1967;2(7526):1105–7. DOI: 10.1016/s0140-6736(67)90615-0

24. Popescu F.D., Vieru M. Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules. World J Methodol 2018;8(3):17–36. DOI: 10.5662/wjm.v8.i3.17

25. Lis K., Bartuzi Z. Selected technical aspects of molecular allergy diagnostics. Curr Issues Mol Biol 2023;45(7):5481–93. DOI: 10.3390/cimb45070347

26. Maesa J.M., Dobrzynska A., Baños-Álvarez E. et al. ImmunoCAP ISAC in food allergy diagnosis: a systematic review of diagnostic test accuracy. Clin Exp Allergy 2021;51(6):778–89. DOI: 10.1111/cea.13871

27. Melioli G., Bonifazi F., Bonini S. et al. The ImmunoCAP ISAC molecular allergology approach in adult multi-sensitized Italian patients with respiratory symptoms. Clin Biochem 2011;44(12):1005–11. DOI: 10.1016/j.clinbiochem.2011.05.007

28. Lupinek C., Marth K., Niederberger V. et al. Analysis of serum IgE reactivity profiles with microarrayed allergens indicates absence of de novo IgE sensitizations in adults. J Allergy Clin Immunol 2012;130(6):1418–20.e4. DOI: 10.1016/j.jaci.2012.06.028

29. Cabrera-Freitag P., Goikoetxea M.J., Beorlegui C. et al. Can component-based microarray replace fluorescent enzimoimmunoassay in the diagnosis of grass and cypress pollen allergy? Clin Exp Allergy 2011;41(10):1440–6. DOI: 10.1111/j.1365-2222.2011.03818.x

30. Heffler E., Puggioni F., Peveri S. et al. Extended IgE profile based on an allergen macroarray: a novel tool for precision medicine in allergy diagnosis. World Allergy Organ J. 2018;11(1):7. DOI: 10.1186/s40413-018-0186-3

31. Kochuyt A.M., Van Hoeyveld E.M., Stevens E.M. Prevalence and clinical relevance of specific immunoglobulin E to pollen caused by sting‐induced specific immunoglobulin E to crossreacting carbohydrate determinants in Hymenoptera venoms. Clin Exp Allergy 2005;35(4):441–7. DOI: 10.1111/j.1365-2222.2005.02217.x

32. Malandain H., Giroux F., Cano Y. The influence of carbohydrate structures present in common allergen sources on specific IgE results. Eur Ann Allergy Clin Immunol 2007;39(7):216–20. PMID: 18236996

33. Mari A. IgE to cross-reactive carbohydrate determinants: analysis of the distribution and appraisal of the in vivo and in vitro reactivity. Int Arch Allergy Immunol 2002;129(4):286–95. DOI: 10.1159/000067591

34. Altmann F. Coping with cross-reactive carbohydrate determinants in allergy diagnosis. Allergo J Int 2016;25(4):98–105. DOI: 10.1007/s40629-016-0115-3

35. Platteel A.C.M., van der Pol P., Murk J.L. et al. A comprehensive comparison between ISAC and ALEX2 multiplex test systems. Clin Chem Lab Med 2022;60(7):1046–52. DOI: 10.1515/cclm-2022-0191

36. Nerelius C., Andersson M., Sogaard L. et al. Comparative study of Allergy Explorer (ALEX) versus ImmunoCAP platforms. Rossiyskiy allergologicheskiy zhurnal = Russian Journal of Allergy 2020;17(1):66–84. (In Russ.). DOI:10.36691/RAJ.2.020.17.1.007

37. Gattinger P., Huang H.J., Valenta R., Vrtala S. Response to González-Pérez et al. J Invest Dermatol 2022;142(3 Pt A): 723–6. DOI: 10.1016/j.jid.2021.09.006

38. González-Pérez R., Poza-Guedes P., Pineda F. et al. Atopic dermatitis and frequency of Der p 11 binding as a major allergen revisited. J Invest Dermatol 2022;142(3 Pt A):721–3. DOI: 10.1016/j.jid.2021.05.037

39. Murrison L.B., Brandt E.B., Myers J.B. et al. Environmental exposures and mechanisms in allergy and asthma development. J Clin Invest 2019;129(4):1504–15. DOI: 10.1172/JCI124612

40. Luo W., Wang D., Zhang T. et al. Prevalence patterns of allergen sensitization by region, gender, age, and season among patients with allergic symptoms in mainland China: A four-year multicenter study. Allergy 2021;76(2):589–93. DOI: 10.1111/all.14597

41. Krishna M.T., Mahesh P.A., Vedanthan P. et al. An appraisal of allergic disorders in India and an urgent call for action. World Allergy Organ J 2020;13(7):100446. DOI: 10.1016/j.waojou.2020.100446

42. Kiewiet M.B.G., Lupinek C., Vrtala S. et al. A molecular sensitization map of European children reveals exposomeand climate-dependent sensitization profiles. Allergy 2023;78(7):2007–18. DOI: 10.1111/all.15689

43. Trofimenko S., Rakova K. Pollen allergy in Rostov-on-Don. Rossiysksya rinologiya = Russian Rhinology 2015;23(1):36–9. (In Russ.). DOI: 10.17116/rosrino201523136-39

44. Lebedenko A.A., Semernik O.E., Yanchenko V.V. et al. The spectrum of pollen sensitization in children with allergic diseases living in the Rostov region. Meditsinskiy vestnik yuga Rossii = Medical Herald of the South of Russia 2023;14(1):50–5. (In Russ.). DOI: 10.21886/2219-8075-2023-14-1-50-55

45. Shamgunova B., Chuykova D., Zaklyakova L. Сlinical and epidemiological characteristics of hay fever in adults of Astrakhan region. Astrakhanskiy meditsinskiy zhurnal = Astrakhan Medical Journal 2010;4:73–8. (In Russ.).

46. Nilova M., Tush E., Eliseeva T. и др. Structure of sensibilization to aeroallergenes in children with atopic bronchial asthma. Allergologiya y immunologiya v pediatrii = Allergology and Immunology in Pediatrics 2019;2(57):17–23. (In Russ.). DOI: 10.24411/2500-1175-2019-00008

47. Smolkin Yu.S., Masalskiy S.S., Zaytseva G.V., Smolkina O.Yu. Аllergic sensitization in children with atopic dermatitis in the first 2 years of life according to the results of skin tests. Voprosy pitaniia = Problems of Nutrition 2022;91(6):50–60. DOI: 10.33029/0042-8833-2022-91-6-50-60. (In Russ.).

48. Elisyutina O., Lupinek C., Fedenko E. et al. IgE-reactivity profiles to allergen molecules in Russian children with and without symptoms of allergy revealed by micro-array analysis. Pediatr Allergy Immunol 2021;32(2):251–63. DOI: 10.1111/pai.13354

49. Shakhova N.V., Kamaltynova E.M., Lobanov Yu.F. et al. The prevalence of allergic and non-allergic bronchial asthma and the spectrum of sensitization among children of preschool age living in urban areas of the Altai Territory: a momentary population study. Rossiyskiy vestnik perinatologii i pediatrii = Russian Bulletin of Perinatology and Pediatrics 2019;64(1):88–93. (In Russ.). DOI: 10.21508/1027-4065-2019-64-1-88-93

50. Vahnina O.A., Zainullina K.S. Etiological spectrum of pollen allergens in patients with pollinosis in the Komi Republic. Prakticheskaya meditsina = Practical Medicine 2012; 6(61):69–72. (In Russ.).

51. Macharadze D. Some features of the prevalence of respiratory allergy in southern Russia. Rossiyskiy allergologicheskiy zhurnal = Russian Journal of Allergy 2019;18:23–8. (In Russ.). DOI: 10.36691/RJA17

52. Gushchin M.O. On sensitization of school-age children to pollen grains of plants in the Perm region. In: Young Science in practical healthcare: proceedings of the 92nd final Scientific and practical Conference of students, residents, postgraduates, young scientists (under 35 years old) Russian State Medical University named after Academician E.A. Wagner, Perm, April 15–16, 2019. Perm: Perm State Medical University named after Academician E.A. Wagner, 2019; p. 133–4. (In Russ.).

53. Yakovleva M.V., Lykina T.A. Sensitization factors when rhinitis is included in Kursk region. In: Materials of the 75th All-Russian Scientific Conference of students and young scientists with international participation: Youth science and modernity, dedicated to the 75th anniversary of KSMU. Kursk: KSMU, 2010; p. 46–7. (In Russ.).

54. Ivanova O.N. Analysis of the incidence of allergic rhinitis among children in the Sakha Republic (Yakutia). Vestnik Severo-Vostochnogo federalnogo universiteta im. M.K. Ammosova. Seria meditsinskie nauki = Bulletin of the Northeastern Federal University named after M.K. Ammosov. Medical Sciences Series 2017;3(08):12–6. (In Russ.).

55. Andronova E.V., Lepeshkova T.S. Sensitization peculiarities for children with allergic rhinitis living in Magnitogorsk and Beloretsk cities. Allergologia y immunologiya v pediatrii = Allergology and Immunology in Pediatrics 2022;4:14–21. (In Russ.). DOI: 10.53529/2500-1175-2022-4-14-21

56. Valenta R., Karaulov A., Niederberger V. et al. Allergen extracts for in vivo diagnosis and treatment of allergy: is there a future? J Allergy Clin Immunol Pract 2018;6(6):1845–55.e2. DOI: 10.1016/j.jaip.2018.08.032