IL4受体α突变与哮喘发作及肥大细胞数量IgE表达相关
2007/06/27
既往研究表明IL4受体α突变与肺功能低下及血清高水平IgE相关。本研究观察了IL4受体α突变与哮喘发作、肺功能及气道组织炎症细胞浸润的关系。采用2个队列研究，分析了IL4受体α的5个单核苷酸多态性与哮喘发作、肺功能及组织炎症浸润。结果表明：E375A and Q551R与非洲美国人哮喘发作及低肺功能相关；E375A 与气道炎症细胞浸润及血清IgE相关。
作者认为IL4受体α突变与非洲美国人哮喘发作及肥大细胞数量IgE表达相关。
作者认为IL4受体α突变与非洲美国人哮喘发作及肥大细胞数量IgE表达相关。
（刘颖格 西安,第四军医大学西京医院呼吸内科 710032 摘译）
( Am J Respir Crit Care Med ,2007,175:570–576)
IL4Rα Mutations Are Associated with Asthma Exacerbations and Mast Cell/IgE Expression
Sally E. Wenzel1, Silvana Balzar1, Elizabeth Ampleford2, Gregory A. Hawkins2, William W. Busse3, William J. Calhoun4, Mario Castro5, K. Fan Chung6, Serpil Erzurum7, Benjamin Gaston8, Elliot Israel9, W. Gerald Teague10, Douglas Curran-Everett11, Deborah A. Meyers2 and Eugene R. Bleecker2
ABSTRACT
Background: Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor α (IL4Rα ) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown.
Hypothesis: Allelic substitutions in IL4Rα are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE.
Methods: Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Rα . These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE.
Results: In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately.
Conclusions: SNPs in IL4Rα , which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell–related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.
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