Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis

Makino, Yuka; Noguchi, Emiko; Takahashi, Noboru; Matsumoto, Yuri; Kubo, Seita; Yamada, Takechiyo; Imoto, Yoshimasa; Ito, Yumi; Osawa, Yoko; Shibasaki, Masanao; Uchida, Kazuhiko; Meno, Kohji; Suzuki, Hideaki; Okubo, Kimihiro; Arinami, Tadao; Fujieda, Shigeharu

doi:10.1016/j.jaci.2010.06.031

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 126, Issue 6 , Pages 1163-1169.e5, December 2010

Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis

Yuka Makino, MS
- Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Emiko Noguchi, MD, PhD
- Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
- Reprint requests: Emiko Noguchi, MD, PhD, Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-city, Ibaraki, Japan.
Noboru Takahashi, MD, PhD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Yuri Matsumoto, MS
- Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Seita Kubo, MD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Takechiyo Yamada, MD, PhD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Yoshimasa Imoto, MD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Yumi Ito, MD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Yoko Osawa, MD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Masanao Shibasaki, MD
- Department of Pediatrics, Tsukuba University of Technology; University of Tsukuba, Ibaraki, Japan
Kazuhiko Uchida, PhD
- Department of Molecular Biological Oncology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Kohji Meno, PhD
- Department of Molecular Biological Oncology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Hideaki Suzuki, BA
- Department of Molecular Biological Oncology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Kimihiro Okubo, MD, PhD
- Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan
Tadao Arinami, MD, PhD
- Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Shigeharu Fujieda, MD, PhD
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

Received 2 March 2010; received in revised form 18 June 2010; accepted 28 June 2010. published online 01 September 2010.

Background

Allergic rhinitis is a global health problem that causes major illnesses and disability worldwide. Allergen-specific immunotherapy (SIT) is the only available treatment that can alter the natural course of allergic disease. However, the precise mechanism underlying allergen-SIT is not well understood.

Objective

The aim of the current study was to identify protein expression signatures reflective of allergen-SIT—more specifically, sublingual immunotherapy (SLIT).

Methods

Serum was taken twice from patients with seasonal allergic rhinitis caused by Japanese cedar: once before the pollen season and once during the season. A total of 25 patients was randomly categorized into a placebo-treated group and an active-treatment group. Their serum protein profiles were analyzed by 2-dimensional electrophoresis.

Results

Sixteen proteins were found to be differentially expressed during the pollen season. Among the differentially expressed proteins, the serum levels of complement C4A, apolipoprotein A-IV (apoA-IV), and transthyretin were significantly increased in SLIT-treated patients but not in placebo-treated patients. Among these proteins, the serum levels of apoA-IV correlated with the clinical symptom-medication scores (r = –0.635; P < .05) and with quality of life scores (r = –0.516; P < .05) in the case of SLIT-treated patients. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium (P < .01).

Conclusion

Our data will increase the understanding of the mechanism of SLIT and may provide novel insights into the treatment of allergic rhinitis.

Key words: Sublingual immunotherapy, apoA-IV, HNF4A, proteome

Abbreviations used: ApoA-IV, Apolipoprotein A-IV, 2-DE, Two-dimensional polyacrylamide gel electrophoresis, HNF4A, Hepatocyte nuclear factor 4α, HRP, Horseradish peroxidase, JAU, Japanese allergy unit, JC, Cryptomeria japonica, JRQLQ, Juniper Rhinoconjunctivitis Quality-of-Life Questionnaire, MALDI-TOF/TOF, Matrix laser desorption/ionization 2-stage time-of-flight, QOL, Quality of life, SAR, Seasonal allergic rhinitis, SIT, Specific immunotherapy, SLIT, Sublingual immunotherapy, SMS, Symptom-medication score

Supported by a Grant-in-Aid for Scientific Research from the Ministry of Health and Welfare, Japan (H17-Genome-001, H17-Immunology-001, H20-Immunology-001, -004) and from the Ministry of Education, Science and Culture of Japan (17390458, 18591097, 20390441).

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(10)01033-X

doi:10.1016/j.jaci.2010.06.031

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 126, Issue 6 , Pages 1163-1169.e5, December 2010

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