Allergy Asthma Respir Dis.  2016 Jul;4(4):264-270. 10.4168/aard.2016.4.4.264.

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

• Kim SH
• Yang EM
• Jung HM
• Pham DL
• Choi HN
• Ban GY
• Park HS

• KMID: 2346755
• DOI: http://doi.org/10.4168/aard.2016.4.4.264

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 (r 2=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.

Keyword

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

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
Immunoglobulin G
RNA, Double-Stranded
Toll-Like Receptor 3

Figure

• 

  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.

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