Allergy Asthma Respir Dis.  2018 Jul;6(4):191-196. 10.4168/aard.2018.6.4.191.

Allergen standardization

• Park JW
• Jeong KY

• KMID: 2417845
• DOI: http://doi.org/10.4168/aard.2018.6.4.191

Abstract

Allergen immunotherapy (AIT) and diagnostic tests are based on well qualified allergen extracts, which are derived from biologic organisms. The allergenicity of the extracts is markedly affected by the climate, soil, year of production, storage methods, and manufacturing processes. Thus, standardization is a crucial process to guarantee the clinical efficacy and safety of the treatment and diagnostic reagents in allergic diseases. There are 2 different standardization processes, one is In vivo and the other is in vitro standardization. In vivo standardization is done by skin prick or intradermal tests. For in vitro standardization, measurements of weight/volume and protein nitrogen units have been widely used since the early period of AIT. In the 1970s, immunological methods such as radial immunodiffusion, enzyme-linked immunosorbent assay (ELISA) inhibition test and basophil activation test were developed. Allergen potency measured by ELISA inhibition test reflects the potency measured by skin tests and has been widely used for quality control of batch-to-batch variation. Recently, standardizations focused on the major allergen content of extracts have developed. Standardization for major allergens requires reliable reference materials (RMs) made of recombinant allergens and 2-site ELISA kits. However, only a few reliable RM and 2-site ELISA kits are available. For the standardization process, allergen RMs are essential. The Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration provides 19 allergen RMs, and our research team also proved 9 RMs which are important in Korea. In conclusion, allergen standardization is an essential process for the development of reliable treatment and diagnostic reagents, and allergy specialist should be familiar with the concept of allergen standardization.

Keyword

Allergen standardization; Allergen immunotherapy; Reference material

MeSH Terms

Allergens
Basophils
Biological Products
Climate
Desensitization, Immunologic
Diagnostic Tests, Routine
Enzyme-Linked Immunosorbent Assay
Hypersensitivity
Immunodiffusion
In Vitro Techniques
Indicators and Reagents
Intradermal Tests
Korea
Nitrogen
Quality Control
Skin
Skin Tests
Soil
Specialization
Treatment Outcome
United States Food and Drug Administration
Allergens
Biological Products
Indicators and Reagents
Nitrogen
Soil

Reference

1. Noon L. Preophylaxctic inoculation against hay fever. Lancet. 1911; 177:1572–3.

2. Esch RE. Allergen source materials and quality control of allergenic extracts. Methods. 1997; 13:2–13.

3. Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015; 136:556–68.

4. Slater JE, Menzies SL, Bridgewater J, Mosquera A, Zinderman CE, Ou AC, et al. The US Food and Drug Administration review of the safety and effectiveness of nonstandardized allergen extracts. J Allergy Clin Immunol. 2012; 129:1014–9.

5. Slater JE, Esch RE. Preparation and standardization ofallergen extracts. Adkinson NF, Bochner BS, Burks W, Busse WW, Holgate ST, Lemanske RF, editors. Middleton's allergy: principle and practice. 8th ed.Philadelphia (PA): Elsevier/Saunders;2014. p. 470–81.

6. Codina R, Crenshaw RC, Lockey RF. Considerations about pollen used for the production of allergen extracts. J Allergy Clin Immunol Pract. 2015; 3:676–82.

7. Jeong KY, Son M, Choi SY, Park KH, Park HJ, Hong CS, et al. Standardization of weed pollen extracts, Japanese hop and mugwort, in Korea. Yonsei Med J. 2016; 57:399–406.

8. Zimmer J, Vieths S, Kaul S. Standardization and regulation of allergen products in the European Union. Curr Allergy Asthma Rep. 2016; 16:21.

9. Park KH, Lee SC, Son YW, Jeong KY, Shin YS, Shin JU, et al. Different responses in induction of allergen specific immunoglobulin G4 and IgE-blocking factors for three mite subcutaneous immunotherapy products. Yonsei Med J. 2016; 57:1427–34.

10. Henmar H, Lund G, Lund L, Petersen A, Würtzen PA. Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy. Clin Exp Immunol. 2008; 153:316–23.

11. Reuter A, Lüttkopf D, Vieths S. New frontiers in allergen standardization. Clin Exp Allergy. 2009; 39:307–9.

12. Dreborg S. Precision of biological standardization of allergenic prepara-tions. Allergy. 1992; 47(4 Pt 1):291–4.

13. Turkeltaub PC. Biological standardization of allergenic extracts. Allergol Immunopathol (Madr). 1989; 17:53–65.

14. May JC, Sih JT, Miller JR, Seligmann EB Jr. Optimization of parameters in protein nitrogen unit precipitation procedure for allergenic extracts. J Allergy Clin Immunol. 1979; 63:87–97.

15. Cooks RA, Stull A. The preparation and standardization of pollen extracts for the treatment of hay fever. J Allergy Clin Immunol. 1933; 4:87–91.

16. Vereda A, van Hage M, Ahlstedt S, Ibañez MD, Cuesta-Herranz J, van Odijk J, et al. Peanut allergy: clinical and immunologic differences among patients from 3 different geographic regions. J Allergy Clin Immunol. 2011; 127:603–7.

17. 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; 70:1393–405.

18. King TP, Norman PS, Connell JT. Isolation and characterization of allergens from ragweed pollen. II. Biochemistry. 1964; 3:458–68.

19. Cox L, Li JT, Nelson H, Lockey R. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunl. 2007; 120(3 Suppl):S25–85.

20. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998; 102(4 Pt 1):558–62.

21. Park JW, Kim KS, Jin HS, Kim CW, Kang DB, Choi SY, et al. Der p 2 isoallergens have different allergenicity, and quantification with 2-site ELISA using monoclonal antibodies is influenced by the isoallergens. Clin Exp Allergy. 2002; 32:1042–7.

22. Jeong KY, Jin HS, Oh SH, Hong CS, Lee IY, Ree HI, et al. Monoclonal antibodies to recombinant Der f 2 and development of a two-site ELISA sensitive to major Der f 2 isoallergen in Korea. Allergy. 2002; 57:29–34.

23. Grier TJ, Hazelhurst DM, Duncan EA, West TK, Esch RE. Major allergen measurements: sources of variability, validation, quality assurance, and utility for laboratories, manufacturers, and clinics. Allergy Asthma Proc. 2002; 23:125–31.

24. Ferreira F, Wolf M, Wallner M. Molecular approach to allergy diagnosis and therapy. Yonsei Med J. 2014; 55:839–52.

25. van Ree R, Chapman MD, Ferreira F, Vieths S, Bryan D, Cromwell O, et al. The CREATE project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergy. 2008; 63:310–26.

26. Kaul S, Zimmer J, Dehus O, Costanzo A, Daas A, Buchheit KH, et al. Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1. Allergy. 2016; 71:1414–24.

27. Spiric J, Schulenborg T, Schwaben L, Engin AM, Karas M, Reuter A. Model for quality control of allergen products with mass spectrometry. J Pro-teome Res. 2017; 16:3852–62.

28. Carnés J, Himly M, Gallego M, Iraola V, Robinson DS, Fernández-Caldas E, et al. Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba. Clin Exp Allergy. 2009; 39:426–34.

29. Tscheppe A, Breiteneder H. Recombinant allergens in structural biology, diagnosis, and immunotherapy. Int Arch Allergy Immunol. 2017; 172:187–202.

30. Morrow KS, Slater JE. Regulatory aspects of allergen vaccines in the US. Clin Rev Allergy Immunol. 2001; 21:141–52.

31. Jeong KY, Choi SY, Lee JH, Lee IY, Yong TS, Lee JS, et al. Standardization of house dust mite extracts in Korea. Allergy Asthma Immunol Res. 2012; 4:346–50.

32. Jeong KY, Choi SY, Lee JH, Lee JS, Yong TS, Hong CS, et al. Preparation and characterization of an extract of german cockroach from a korean source. Allergy Asthma Immunol Res. 2013; 5:102–5.

33. Jeong KY, Yi MH, Son M, Lyu D, Lee JH, Yong TS, et al. IgE reactivity of recombinant Pac c 3 from the Asian needle ant (Pachycondyla chinensis). Int Arch Allergy Immunol. 2016; 169:93–100.

34. Jeong KY, Lee JH, Kim EJ, Lee JS, Cho SH, Hong SJ, et al. Current status of standardization of inhalant allergen extracts in Korea. Allergy Asthma Immunol Res. 2014; 6:196–200.

35. Helm RM, Gauerke MB, Baer H, L⊘wenstein H, Ford A, Levy DA, et al. Production and testing of an international reference standard of short ragweed pollen extract. J Allergy Clin Immunol. 1984; 73:790–800.

36. Ford A, Seagroatt V, Platts-Mills TA, L⊘wenstein H. A collaborative study on the first international standard of Dermatophagoides pteronyssinus (house dust mite) extract. J Allergy Clin Immunol. 1985; 75:676–86.