de Las Vecillas Sánchez Leticia, Alenazy Leila A, Garcia-Neuer Marlene, Castells Mariana C
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Allergy, Marqués de Valdecilla University Hospital-IDIVAL, 39011 Santander, Spain.
Int J Mol Sci. 2017 Jun 20;18(6):1316. doi: 10.3390/ijms18061316.
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a "bench to bedside" approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.
在21世纪，随着新型治疗药物的不断涌现，药物超敏反应（HSR）日益增多。癌症、慢性炎症性疾病、囊性纤维化或糖尿病患者在反复接触一线治疗药物后，或通过与环境过敏原的交叉反应，可能会对这些药物产生过敏。避免使用引起过敏的药物可能会影响疾病管理、生活质量和预期寿命。精准医学为理解和管理超敏反应（HSR）提供了新工具，同时也为IgE（免疫球蛋白E）介导和非IgE介导的超敏反应提供了个性化的药物脱敏（DS）治疗方法。DS通过逐步增加引起过敏药物的次优剂量诱导暂时的低反应状态。体外模型已证明，IgE脱敏是一个抗原特异性过程，可阻断钙内流，影响抗原/IgE/FcεRI复合物的内化，并防止急性和迟发性反应以及肥大细胞介质释放。通过“从实验室到临床”的方法，体外脱敏模型有助于阐明DS所涉及的分子途径，为改进所有患者的脱敏方案提供新的见解。本综述的目的是总结关于药物超敏反应、IgE介导的脱敏机制及其临床应用的最新信息。
