阿司匹林加重性呼吸系统疾病患者的HLA - DRB和HLA - DQ基因变异性
HLA-DRB and HLA-DQ genetic variability in patients with aspirin-exacerbated respiratory disease.
作者信息
Esmaeilzadeh Hossein, Nabavi Mohammad, Amirzargar Ali Akbar, Aryan Zahra, Arshi Saba, Bemanian Mohammad Hassan, Fallahpour Morteza, Mortazavi Negar, Rezaei Nima
机构信息
Department of Immunology, Rasool-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Am J Rhinol Allergy. 2015 May-Jun;29(3):e63-9. doi: 10.2500/ajra.2015.29.4154.
BACKGROUND
Major histocompatibility complex (MHC) class II is involved in T-cell activation, cytokine secretion, and induction of immune responses. Cytokines, staphylococcus super antigens, and eosinophil activation are proposed to play important roles in aspirin-exacerbated respiratory disease (AERD).
OBJECTIVES
This study is aimed at investigating the association of HLA-DRB and DQ genetic variabilities in patients with AERD.
METHODS
A genetic association analysis in three different groups, including 33 patients with AERD, 17 patients with aspirin-tolerant asthma (ATA), and 100 healthy controls was performed. Oral aspirin challenge (OAC) test was performed to identify aspirin hypersensitivity. Pulmonary function test (PFT) was performed for all patients. Eosinophil percentage in nasal smear and peripheral blood and serum immunoglobin (Ig)E were investigated. HLA-DRB, HLA-DQA1, and HLA-DQB1 were genotyped using polymerase chain reaction.
RESULTS
HLA-DQB10302 (OR, 5.49, 95% confidence interval [CI],(2.40-12.59)), HLA-DQA10301 (OR, 2.90, 95% CI, (1.49-5.67)), HLA-DRB4 (OR, 2.94, 95% CI, (1.61-5.36)), and HLA-DRB104 (OR, 3.19, 95% CI, (1.57-6.47)) were higher in patients with AERD compared with controls. In patients with AERD, HLA-DQB10301 (OR,0.22, 95% CI, (0.09-0.54)), HLA-DQA10501 (OR, 0.42, 95% CI, (0.21-0.81)), HLA-DRB111 (OR, 0.30, 95% CI, (0.12-0.73)), and HLA-DRB3 (OR, 0.38, 95% CI, (0.21-0.70)) were significantly lower compared with healthy controls. Patients with AERD had lower frequencies of HLA-DQB10301 (OR, 0.27, 95% CI, (0.08-0.86)), and HLA-DRB1011 (OR, 0.27, 95% CI, (0.08-0.86)) compared with ATA. Haplotypes of HLA-DRB104/ DQA10301/ DQB10302 (OR, 4.25, 95% CI, (1.94-9.29)) and HLA-DRB107 /DQA10201/ DQB10201 (OR, 3.52, 95% CI, (1.54-8.06)) were higher in patients with AERD compared with controls (all p < 0.05).
CONCLUSIONS
Results of this study suggest that HLA-DQB10302 and HLA-DRB104 and their related haplotypes are genes involved in predisposing patients to AERD, whereas HLA-DQB10301 and HLA-DRB1011 have negative association with AERD.
背景
主要组织相容性复合体（MHC）II类分子参与T细胞活化、细胞因子分泌及免疫反应的诱导。细胞因子、葡萄球菌超抗原及嗜酸性粒细胞活化被认为在阿司匹林加重的呼吸系统疾病（AERD）中起重要作用。
目的
本研究旨在调查AERD患者中HLA-DRB和DQ基因变异的相关性。
方法
对三组不同人群进行基因关联分析，包括33例AERD患者、17例阿司匹林耐受哮喘（ATA）患者和100例健康对照。进行口服阿司匹林激发试验（OAC）以确定阿司匹林超敏反应。对所有患者进行肺功能测试（PFT）。检测鼻涂片和外周血中嗜酸性粒细胞百分比及血清免疫球蛋白（Ig）E。采用聚合酶链反应对HLA-DRB、HLA-DQA1和HLA-DQB1进行基因分型。
结果
与对照组相比，AERD患者中HLA-DQB10302（比值比[OR]，5.49，95%置信区间[CI]，(2.40 - 12.59)）、HLA-DQA10301（OR，2.90，95% CI，(1.49 - 5.67)）、HLA-DRB4（OR，2.94，95% CI，(1.61 - 5.36)）和HLA-DRB104（OR，3.19，95% CI，(1.57 - 6.47)）的频率更高。在AERD患者中，与健康对照相比，HLA-DQB10301（OR，0.22，95% CI，(0.09 - 0.54)）、HLA-DQA10501（OR，0.42，95% CI，(0.21 - 0.81)）、HLA-DRB111（OR，0.30，95% CI，(0.12 - 0.73)）和HLA-DRB3（OR，0.38，95% CI，(0.21 - 0.70)）显著降低。与ATA患者相比，AERD患者中HLA-DQB10301（OR，0.27，95% CI，(0.08 - 0.86)）和HLA-DRB1011（OR，0.27，95% CI，(0.08 - 0.86)）的频率较低。与对照组相比，AERD患者中HLA-DRB104 / DQA10301 / DQB10302单倍型（OR，4.25，95% CI，(1.94 - 9. .29)）和HLA-DRB107 / DQA10201 / DQB10201单倍型（OR，3.52，95% CI，(1.54 - 8.06)）的频率更高（所有p < 0.05）。
结论
本研究结果表明，HLA-DQB10302和HLA-DRB104及其相关单倍型是使患者易患AERD的基因，而HLA-DQB10301和HLA-DRB1011与AERD呈负相关。
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