MHC restriction in allergic bronchopulmonary aspergillosis
MHC restriction in allergic bronchopulmonary aspergillosis
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DOI：
10.2741/971
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发表时间：
2003-01-01
期刊：
影响因子：
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通讯作者：
Bellone, CJ
中科院分区：
文献类型：
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作者：
Chauhan, B;Hutcheson, PS;Bellone, CJ
过敏性支气管肺曲霉病（ABPA）是哮喘患者的一种罕见并发症，但在囊性纤维化患者中更为常见。当下呼吸道存在真菌烟曲霉 (Af) 时，患者会产生针对 Af 抗原的特异性 IgG 和 IgE 体液反应。 ABPA 研究表明，抗原特异性 CD4+ Th2 样 T 淋巴细胞产生的 IL-4 和 IL-5 水平升高，具有致病作用。编码高度多态性 HLA 分子的 MHC II 类基因已被证明是控制对常见过敏原的免疫反应的可能候选基因。然而，关于 HLA 基因在 ABPA 发展中的病理生理学作用的信息一直缺乏。这篇综述描述了 HLA-II 类等位基因与 ABPA 中对 Af 抗原 (Asp f 1) 的特异性反应之间的关联。这些研究重点关注两组不相关的患有囊性纤维化和/或哮喘的北美白种人患者中 MHC 限制和 HLA-II 类等位基因的分布。一组由确诊为 ABPA 的患者组成，第二组由对 Af 敏感但无 ABPA 的患者组成。 HLA 关联研究表明，发生 ABPA 的倾向与 HLA-DR2 和 DR5 相关，也可能与 DR4 或 DR7 相关。 HLA-DR 抗原与 ABPA 的强关联反映了 HLA-DR 分子可能呈递致病肽。另一方面，HLA-DQ2 与 Af 敏感的 nonABPA 显着相关，表明 HLA-DQ 分子参与保护。这些遗传因素的组合决定了囊性纤维化和哮喘患者的 ABPA 治疗结果。
Allergic bronchopulmonary aspergillosis (ABPA) is a rare complication in patients with asthma but more common in patients with cystic fibrosis. In the presence of the fungus Aspergillus fumigatus (Af) in the lower respiratory tract, patients mount a heightened IgG and IgE humoral response specific for Af antigens. Studies on ABPA have suggested a pathogenic role for antigen specific CD4+ Th2 like T lymphocytes producing increased levels of IL-4 and IL-5. MHC class II genes coding for highly polymorphic HLA molecules have been shown to be the likely candidates for controlling immune responses to common allergens. However there has been a lack of information on the pathophysiological role of HLA genes in the development of ABPA.This review describes an association between HLA-class II alleles and the specific responses to Af antigen (Asp f 1) in ABPA. These studies focused on MHC restriction and distribution of HLA-class II alleles in two groups of unrelated North American Caucasian patients with cystic fibrosis and/or asthma. One group consisted of patients with a confirmed diagnosis of ABPA and a second group of patients with Af sensitivity but no ABPA. HLA association studies revealed that the predisposition to develop ABPA is associated with HLA-DR2 and DR5, and possibly DR4 or DR7. A strong association of HLA-DR antigens with ABPA reflects that HLA-DR molecules may present disease-causing peptides. On the other hand a significant association of HLA-DQ2 with Af sensitive nonABPA indicates the involvement of HLA-DQ molecules in protection. A combination of these genetic factors determines the outcome of ABPA in patients with cystic fibrosis and asthma.