Yonsei Med J.  2018 Sep;59(7):852-856. 10.3349/ymj.2018.59.7.852.

IgE Cross-Reactivity between Humulus japonicus and Humulus lupulus

  • 1Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea. parkjw@yuhs.ac, jeongky@yuhs.ac
  • 2Research and Development Department, Lofarma S.p.A, Viale Cassala, Milan, Italy.


Japanese hop (Humulus japonicus) is a major cause of weed pollinosis in East Asia. However, supplies of commercial allergen extract from this plant have not met clinical demand. The pollen of common hop (Humulus lupulus), a closely related species, may provide an alternative source if there is strong IgE cross-reactivity between these two species. We aimed to compare the IgE cross-reactivity and allergenicity of common hop and Japanese hop pollen.
Cross-reactivity was measured by inhibition ELISA. One- and two-dimensional (2D) gel analyses combined with IgE immunoblotting and mass spectrometry [liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)] were performed to detect IgE-reactive pollen components.
Up to 16.7% of IgE reactivity to Japanese hop was inhibited by common hop. A 12-kDa protein component of Japanese hop pollen that showed the most potent IgE reaction was absent from common hop. Six IgE-reactive components from Japanese hop were detected by 2D gel electrophoresis and LC-ESI-MS/MS, but showed low Mascot scores, preventing positive identification.
No significant IgE cross-reaction was observed for Japanese and common hop pollen allergens. Development of allergy diagnostic and immunotherapeutic reagents based on Japanese hop pollen are urgently needed.


Allergen; cross-reactivity; Japanese hop; pollinosis; pollen

MeSH Terms

Asian Continental Ancestry Group
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Equipment and Supplies
Far East
Immunoglobulin E*
Indicators and Reagents
Mass Spectrometry
Rhinitis, Allergic, Seasonal
Tandem Mass Spectrometry
Immunoglobulin E
Indicators and Reagents


  • Fig. 1 Inhibition ELISA analysis of hop pollen extracts. IgE reactivity to Japanese hop was competitively inhibited by pre-incubation of serum with various concentration of Japanese hop or common hop pollen extracts.

  • Fig. 2 Protein profiles and IgE-reactive components of hop pollen extracts. (A) Proteins (20 µg) were separated on an 18% SDS-PAGE gel under denaturing conditions. (B) IgE-reactive components were probed with serum from Japanese hop allergy patients. J, Japanese hop; L, common hop.

  • Fig. 3 Proteomic analysis of hop pollen proteins. Proteins (50 µg) were separated and visualized with Coomassie Blue stain, and IgE-reactive components were probed with serum from Japanese hop allergy patients. (A) Japanese hop protein profiles. (B) Common hop protein profiles. (C) IgE-reactive components of Japanese hop. (D) IgE-reactive components of common hop. Proteins indicated with arrows were excised and subjected to liquid chromatography coupled to electrospray ionization tandem mass spectrometry analysis.


1. Park HS, Nahm DH, Suh CH, Lee SM, Choi SY, Jung KS, et al. Evidence of Hop Japanese pollinosis in Korea: IgE sensitization and identification of allergenic components. J Allergy Clin Immunol. 1997; 100:475–479. PMID: 9338540.
2. Park HJ, Lee JH, Park KH, Kim KR, Han MJ, Choe H, et al. A six-year study on the changes in airborne pollen counts and skin positivity rates in Korea: 2008–2013. Yonsei Med J. 2016; 57:714–720. PMID: 26996572.
3. Wang XY, Ma TT, Wang XY, Zhuang Y, Wang XD, Ning HY, et al. Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China. Allergy. 2018; 73:1232–1243. PMID: 29322523.
4. Cui L, Yin J. Association of serum specific IgE levels with asthma in autumn pollen-induced allergic rhinitis: a retrospective analysis. J Asthma. 2018; 4. 18. [Epub]. DOI: 10.1080/02770903.2018.1466316.
5. 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. PMID: 26847293.
6. Codina R, Crenshaw RC, Lockey RF. Considerations about pollen used for the production of allergen extracts. J Allergy Clin Immunol Pract. 2015; 3:676–682. PMID: 26004305.
7. Esch RE. Allergen source materials and quality control of allergenic extracts. Methods. 1997; 13:2–13. PMID: 9281463.
8. Spiewak R, Gòra A, Dutkiewicz J. Work-related skin symptoms and type I allergy among eastern-Polish farmers growing hops and other crops. Ann Agric Environ Med. 2001; 8:51–56. PMID: 11426925.
9. Reeb-Whitaker CK, Bonauto DK. Respiratory disease associated with occupational inhalation to hop (Humulus lupulus) during harvest and processing. Ann Allergy Asthma Immunol. 2014; 113:534–538. PMID: 25216973.
10. Jung CG, Yang EM, Lee JH, Kim HM, Park HS. Evaluation of the allergenic relationship between Humulus japonicus and Humulus lupulus pollen allergens. Allergy Asthma Respir Dis. 2017; 5:217–222.
11. Park JW, Ko SH, Kim CW, Jeoung BJ, Hong CS. Identification and characterization of the major allergen of the Humulus japonicus pollen. Clin Exp Allergy. 1999; 29:1080–1086. PMID: 10457112.
12. Burastero SE. Pollen-cross allergenicity mediated by panallergens: a clue to the patho-genesis of multiple sensitizations. Inflamm Allergy Drug Targets. 2006; 5:203–209. PMID: 17168790.
13. Tao AL, He SH. Cloning, expression, and characterization of pollen allergens from Humulus scandens (Lour) Merr and Ambrosia artemisiifolia L. Acta Pharmacol Sin. 2005; 26:1225–1232. PMID: 16174439.
14. Jeong KY, Han IS, Choi SY, Lee JH, Lee JS, Hong CS, et al. Allergenicity of recombinant profilins from Japanese hop, Humulus japonicus. J Investig Allergol Clin Immunol. 2013; 23:345–350.
15. Hong Q, Zhou S, Zhao H, Peng J, Li Y, Shang Y, et al. Allergenicity of recombinant Humulus japonicus pollen allergen 1 after combined exposure to ozone and nitrogen dioxide. Environ Pollut. 2018; 234:707–715. PMID: 29241157.
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