Open Access, Peer-reviewed
pISSN 2288-0402
eISSN 2288-0410
    Allergy Asthma Respir Dis. 2016 Jul;4(4):264-270. Korean.
    Published online Jul 31, 2016.
    https://doi.org/10.4168/aard.2016.4.4.264
    © 2016 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology
    Original Article

    Association of TLR3 gene polymorphism with IgG subclass deficiency and the severity in patients with aspirin-intolerant asthma

    Seung-Hyun Kim,1,2 Eun-Mi Yang,2 Hye-Min Jung,2 Duy Le Pham,1 Hyun-Na Choi,2 Ga-Young Ban,1 and Hae-Sim Park1,2
      • 1Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
      • 2Clinical Trial Center, Ajou University Hospital, Suwon, Korea.
    • Correspondence to: Hae-Sim Park. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: +82-31-219-5196, Fax: +82-31-219-4407, Email: hspark@ajou.ac.kr
    Received October 30, 2015; Revised May 25, 2016; Accepted May 31, 2016.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

    Abstract

    Purpose

    Toll-like receptor 3 (TLR3) recognizes to viral double-stranded RNA and is involved in antiviral defenses. A probable role of TLR3 gene variants in the pathogenesis of aspirin-intolerant asthma (AIA) has been suggested. AIA patients present more frequent asthma exacerbations in which respiratory viral infections could be an exacerbating factor. IgG subclass deficiency was commonly present with bronchial asthma. Based on previous findings, we investigated whether TLR3 variants could affect IgG3 subclass deficiency in AIA.

    Methods

    We enrolled 279 AIA patients, 403 aspirin-tolerant asthma (ATA) patients, and 315 normal healthy controls (NC) in this study. TLR3 polymorphism at the promoter region -299698G>T was genotyped. The serum levels of IgG subclasses were determined by the single radial immunodiffusion method. Expressions of IgG3 and TLR3 on Epstein-Barr virus transformed-B cells isolated from asthmatic patients were evaluated by flow cytometry to investigate B-cell functions.

    Results

    The TLR3 -299698 T allele was significantly associated with severity and IgG3 deficiency in the AIA group (P=0.044 and P=0.010, respectively), but not in the ATA group. IgG3 expression on B cells from asthmatics with IgG3 deficiency was significantly lower compared to those without (P=0.025). There was a positive correlation between IgG3 expression levels on B cells and serum IgG3 levels (r2=0.434, P=0.002).

    Conclusion

    These results suggest that the TLR3 -299698G>T polymorphism may be associated with IgG3 subclass deficiency and severity in AIA.

    Keywords
    Asthma; Genetic polymorphism; Immunoglobulin G; Immunodeficiency; Toll-like receptor 3

    Figures

    Fig. 1
    IgG3 expression in the Epstein-Barr virus-transformed B-cell lines isolated from asthmatic patients. (A) IgG3 surface expression on B cells. (B) Correlation between IgG3 expression levels on B cells and IgG3 serum levels. P-values were determined using the independent t-test and Pearson correlation coefficient. The deficiency group included asthmatic patients who had at least one IgG subclass deficiencies; the normal control group included asthmatic patients who did not have any IgG subclass deficiency.

    Tables

    Table 1
    Clinical characteristics of the study subjects

    Table 2
    Distribution of immunoglobulin G subclass deficiency

    Table 3
    Clinical characteristics of asthma patients with IgG subclass deficiency

    Table 4
    Genotype frequency of TLR3 -299698G>T

    Table 5
    Association of immunoglobulin G3 deficiency as well as severe asthma according to the genotype of TLR3 -299698 G>T in AIA group

    Notes

    This research was supported by grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C2628, HI16C0992).

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    MeSH Terms
    Alleles
    Asthma*
    B-Lymphocytes
    Flow Cytometry
    Herpesvirus 4, Human
    Humans
    Immunodiffusion
    Immunoglobulin G*
    Methods
    Polymorphism, Genetic
    Promoter Regions, Genetic
    RNA, Double-Stranded
    Toll-Like Receptor 3
    Metrics
    Share
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