Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers
Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers
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DOI：
10.1016/j.jaci.2017.10.010
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发表时间：
2017-12-01
影响因子：
14.2
通讯作者：
Durham, Stephen R.
中科院分区：
文献类型：
--
作者：
Shamji, Mohamed H.;Durham, Stephen R.
过敏原免疫治疗对IgE依赖性变应性鼻炎和哮喘患者有效。当免疫治疗连续给予3年时，在其停止后的几年内存在持续的临床益处。这种疾病修饰作用是抗原特异性的和抗原驱动的。临床改善伴随着靶器官中效应细胞数量的减少，包括肥大细胞、嗜碱性粒细胞、嗜酸性粒细胞和2型先天性淋巴细胞。免疫治疗导致产生阻断性IgG/IgG（4）抗体，该抗体可抑制通过肥大细胞和嗜碱性粒细胞上的高亲和力IgE受体（Fc ε RI）和B细胞上的低亲和力IgE受体（Fc ε RII）介导的IgE依赖性活化。T（H）2免疫的抑制可由于抗原特异性T细胞的缺失或无反应性、抗原特异性调节性T细胞的诱导或有利于T（H）1应答的免疫偏离而发生。目前尚不清楚改变的长期记忆是否存在于T细胞或B细胞区室中。最近的数据强调了产生IL-10的调节性B细胞和“保护性”抗体的作用，它们可能有助于长期耐受。了解诱导和持久性耐受的潜在机制应确定临床反应的预测生物标志物，并发现新的和更有效的免疫治疗策略。
Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG(4) antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (Fc epsilon RI) on mast cells and basophils and low-affinity IgE receptors (Fc epsilon RII) on B cells. Suppression of T(H)2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigenspecific regulatory T cells; or immune deviation in favor of T(H)1 responses. It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment. Recent data highlight the role of IL-10-producing regulatory B cells and "protective'' antibodies that likely contribute to long-term tolerance. Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy.