Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, 94305, USA.
Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, 94305, USA.
Clin Rev Allergy Immunol. 2018 Oct;55(2):190-204. doi: 10.1007/s12016-018-8678-z.
The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been described for the use of allergen-specific functional IgG4 antibodies, basophil activation and histamine release, and type 2 innate lymphoid cells. There appears to be a promising association between changes in the expression of dendritic cell-associated markers, as well as the use of DNA promoter region methylation patterns in the prediction of allergy status following therapy. The cellular and molecular changes brought about by immunotherapy are still under investigation, but major strides in our understanding are being made.
在过去几十年中，过敏病症的发病率持续上升，针对此类病症的治疗方法也有大量研究。免疫疗法通过驱动复杂的免疫反应变化，是唯一一种具有长期效果的调节免疫系统的疗法，目前用于治疗多种过敏性疾病。最近的研究重点是确定与这些变化相关的生物标志物，这些标志物可能有助于预测接受过敏原免疫疗法（AIT）的患者中具有最高临床疗效的可能性，指导 AIT 停药，并预测症状复发和治疗后需要进行 AIT 加强治疗的情况。在食物过敏中确定此类生物标志物的额外好处是可以替代目前诊断食物过敏的金标准——口服食物挑战。虽然有几种标志物显示出早期的希望，但研究尚未确定一种可以始终预测 AIT 临床反应的标志物。皮肤点刺试验（SPT）和特异性 IgE 通常被用作开始 AIT 和预测随后过敏原挑战期间反应的纳入标准；然而，现有数据表明，这些标志物的变化并不总是与临床改善相关，并且变化范围很广，从而降低了它们预测临床反应的实用性。类似的发现也描述了过敏原特异性功能性 IgG4 抗体、嗜碱性粒细胞活化和组胺释放以及 2 型先天淋巴细胞的使用。在治疗后预测过敏状态时，树突状细胞相关标志物表达的变化以及 DNA 启动子区域甲基化模式的使用之间似乎存在有希望的关联。免疫疗法带来的细胞和分子变化仍在研究中，但我们对其的理解正在取得重大进展。
