HLA-DRB and HLA-DQ Genetic Variability in Patients with Aspirin-Exacerbated Respiratory Disease

Abstract

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-DQB1*0302 (OR, 5.49, 95% confidence interval [CI],(2.40-12.59)), HLA-DQA1*0301 (OR, 2.90, 95%CI,(1.49-5.67)), HLA-DRB4 (OR, 2.94, 95%CI,(1.61-5.36)), and HLA-DRB1*04 (OR, 3.19, 95%CI,(1.57-6.47)) were higher in patients with AERD compared with controls. In patients with AERD, HLA-DQB1*0301 (OR,0.22, 95%CI,(0.09-0.54)), HLA-DQA1*0501 (OR, 0.42, 95%CI, (0.21-0.81)), HLA-DRB1*11 (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-DQB1*0301 (OR, 0.27, 95%CI,(0.08-0.86)), and HLA-DRB1*011 (OR, 0.27, 95%CI,(0.08-0.86)) compared with ATA. Haplotypes of HLA-DRB1*04/DQA1*0301/DQB1*0302 (OR, 4.25, 95%CI,(1.94-9.29)) and HLA-DRB1*07 /DQA1*0201/ DQB1*0201 (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-DQB1*0302 and HLA-DRB1*04 and their related haplotypes are genes involved in predisposing patients to AERD, whereas HLA-DQB1*0301 and HLA-DRB1*011 have negative association with AERD.