An Exploratory Pilot Study of Genetic Marker for IgE-Mediated Allergic Diseases with Expressions of FcεR1α and Cε.
The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of FcεR1 with the allergic phenotype of Cε expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for Cε expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the FcεR1α promoter region (rs2427827 and rs2251746) and allergic features of Cε expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of FcεR1α promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of FcεR1α promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of FcεR1α was significantly increased after Der p2 stimulation in PBMCs with SNPs of the FcεR1α promoter region. Despite the increased Cε mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the FcεR1α promoter region and the wild type. SNPs of FcεR1α promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced FcεR1α mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus.
Center for Translational Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. en65@vghtc.gov.tw.|Department of Bio-Industry Technology, Da Yeh University, Changhua 51591, Taiwan. en65@vghtc.gov.tw.|Department of Medical Technology, Jen Ten College of Medicine, Nursing and Management, Miaoli 35664, Taiwan. en65@vghtc.gov.tw.
En-Chih
EC
Liao
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan. yun0922.tw@yahoo.com.tw.
Ching-Yun
CY
Chang
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan. chiaweih@gmail.com.
Chia-Wei
CW
Hsieh
College of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan. jim0929@msn.com.
Sheng-Jie
SJ
Yu
Center for Translational Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. scyin@vghtc.gov.tw.
Sui-Chu
SC
Yin
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan. jawji@vghtc.gov.tw.|College of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan. jawji@vghtc.gov.tw.|Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taipei 11221, Taiwan. jawji@vghtc.gov.tw.
Jaw-Ji
JJ
Tsai
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000378:metabolism*; D007073:Immunoglobulin E / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D039981:Pyroglyphidae / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics*; D055815:Young Adult
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; C543355:FcepsilonRI alpha-chain, human; D007127:Immunoglobulin Constant Regions; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E