Service Hospitalier Universitaire Pneumologie Physiologie, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
Inserm, CNRS, IAB, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, University Grenoble Alpes, Grenoble, France.
Allergy. 2021 Aug;76(8):2575-2586. doi: 10.1111/all.14820. Epub 2021 Apr 7.
Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate.
To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules.
The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate).
Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB105:01, DQA101:01 and DRB1*01:01, respectively).
Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.
过敏是最常见的免疫紊乱疾病，影响着全球 30%的人口，是免疫球蛋白 E（IgE）对过敏原致敏的结果。在疑似与过敏有关的遗传因素中，HLA Ⅱ类基因组区域是一个强有力的候选者。
评估 HLA Ⅱ类等位基因与对大量呼吸道过敏原分子的特异性 IgE（sIgE）致敏之间的关联。
该分析依赖于 EGEA 队列的 927 名参与者，其中包括 497 名哮喘患者。该研究侧重于 26 种被 sIgE 识别的气传过敏原，这些过敏原在至少 5%的研究人群中被 sIgE 识别（用 MEDALL 芯片检测到 sIgE≥0.3 ISU）和 23 个推断的 HLA Ⅱ类等位基因。对于每个 sIgE 致敏和 HLA Ⅱ类等位基因，我们拟合了一个逻辑回归模型，该模型考虑了家族依赖性，并调整了性别、年龄和遗传主成分。p 值经过多重比较（假发现率）校正。
观察到的 19 个具有统计学意义的关联中，大多数与花粉过敏原有关（艾蒿 Art v 1、橄榄树 Ole e 1、提莫西草 Phl p 2、Phl p 5 和车前草 Pla l 1），有 3 个与霉菌过敏原有关（交链孢霉 Alt a 1），仅有 1 个与屋尘螨过敏原有关（Der p 7）。与宠物过敏原无关。与 mugwort Art v 1 最强的关联（OR=5.42（95%CI，3.30；8.88）、4.14（2.65；6.47）、3.16（1.88；5.31）与 DQB105:01、DQA101:01 和 DRB1*01:01 有关）。
我们的结果支持 HLA Ⅱ类等位基因作为免疫反应基因的重要作用，这些基因使它们的携带者易致敏于各种主要花粉过敏原。
