Ivković-Jureković Irena, Zunec Renata, Balog Vesna, Grubić Zorana
University of Zagreb, "Sestre milosrdnice" University Hospital Center, Children's Hospital Zagreb, Department of Pulmonology, Allergology and Clinical Immunology, Zagreb, Croatia.
Coll Antropol. 2011 Dec;35(4):1243-9.
Allergic asthma is a multifactorial disease involving well known environmental factors and less identified genetic components. In several studies the HLA genes have been implicated in the development of asthma and atopy, but the importance of these associations remains unclear. The aim of the present study was to analyse the distribution of specificities at HLA class I loci (-A and -B) and HLA class II locus (-DRB1) in a group of 143 Croatian children with atopic asthma, regarding total serum IgE and specific IgE against common inhalant allergens, as well as their connection with different asthmatic phenotypes and to identify HLA genotype which increases the risk for atopy or asthma or which has a protective effect. As controls we used a group of 163 healthy unrelated individuals. HLA class I antigens were determined by serology, while DRB1 specificities were detected by polymerase-chain reaction amplification and hybridisation with sequence specific oligonucleotide probes method (PCR-SSOP). We found no significant correlation between any of the HLA-A antigens and asthma, atopy or associated atopic phenotypes. At HLA-B locus, HLA-B8 antigen was significantly increased among asthmatic patients (p = 0.002), patients with high total serum IgE (p = 0.002), as well as among patients sensitizated to Dermatophagoides pteronyssinus (Der p) (p = 0.014) and among patients sensitizated to Der p + Dactylis glomerata (Dact g) or Ambrosia elatior (Amb a) (p = 0.004). Among HLA-DRB1 specificities, HLA-DRB1 01 showed positive correlation with asthma and atopy (p = 0.034), while HLA-DRB103 specificity was observed with significantly higher frequency among patients with total serum IgE > or = 400 KU/L (p = 0.048). HLA-DRB116 specificity was observed with significantly lower frequency among patients with asthma only in comparison to healthy controls (p = 0.027) and to patients with asthma and allergic rhinitis (p = 0.005). In conclusion, our data suggest that HLA specificities play a relevant role in predisposition to asthma, as well as in different clinical forms of atopic diseases. HLA-B8, HLA-DRB101 and HLA-DRB1*03 genotype increases the risk for atopic asthma and high serum IgE.
过敏性哮喘是一种多因素疾病，涉及众所周知的环境因素和尚未明确的遗传成分。在多项研究中，HLA基因与哮喘和特应性的发生有关，但这些关联的重要性仍不明确。本研究的目的是分析143名克罗地亚特应性哮喘儿童中HLA I类基因座（-A和-B）和HLA II类基因座（-DRB1）的特异性分布，涉及总血清IgE和针对常见吸入性变应原的特异性IgE，以及它们与不同哮喘表型的关系，并确定增加特应性或哮喘风险或具有保护作用的HLA基因型。作为对照，我们使用了一组163名健康的无关个体。HLA I类抗原通过血清学方法测定，而DRB1特异性通过聚合酶链反应扩增和与序列特异性寡核苷酸探针杂交方法（PCR-SSOP）检测。我们发现任何HLA-A抗原与哮喘、特应性或相关特应性表型之间均无显著相关性。在HLA-B基因座，哮喘患者（p = 0.002）、总血清IgE水平高的患者（p = 0.002）、对屋尘螨（Der p）致敏的患者（p = 0.014）以及对Der p + 梯牧草（Dact g）或豚草（Amb a）致敏的患者（p = 0.004）中，HLA-B8抗原显著增加。在HLA-DRB1特异性中，HLA-DRB1 01与哮喘和特应性呈正相关（p = 0.034），而在总血清IgE≥400 KU/L的患者中，HLA-DRB103特异性的出现频率显著更高（p = 0.048）。仅患有哮喘的患者中，HLA-DRB116特异性的出现频率与健康对照（p = 0.027）以及哮喘和过敏性鼻炎患者（p = 0.005）相比显著更低。总之，我们的数据表明，HLA特异性在哮喘易感性以及特应性疾病的不同临床形式中发挥相关作用。HLA-B8、HLA-DRB101和HLA-DRB1*03基因型增加了特应性哮喘和高血清IgE的风险。
