Tan Tiak Ju, Delgado-Dolset María I, Escribese María M, Barber Domingo, Layhadi Janice A, Shamji Mohamed H
Immunomodulation and Tolerance Group, Department of National Heart and Lung Institute, Imperial College London, London, UK, and.
Institute of Applied Molecular Medicine (IMMA), Department of Basic Medical Sciences, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, Madrid, Spain.
Allergol Select. 2022 Nov 21;6:267-275. doi: 10.5414/ALX02333E. eCollection 2022.
Allergic rhinitis is an IgE-mediated inflammation that remains a clinical challenge, affecting 40% of the UK population with a wide range of severity from nasal discomfort to life-threatening anaphylaxis. It can be managed by pharmacotherapeutics and in selected patients by allergen immunotherapy (AIT), which provides long-term clinical efficacy, especially during peak allergy season. However, there are no definitive biomarkers for AIT efficacy. Here, we aim to summarize the key adaptive, innate, humoral, and metabolic advances in biomarker identification in response to AIT. Mechanisms of efficacy consist of an immune deviation towards T1-secreting IFN-γ, as well as an induction of IL10 cT and T have been observed. T2 cells undergo exhaustion after AIT due to chronic allergen exposure and correlates with the exhaustion markers PD-1, CTLA-4, TIGIT, and LAG3. IL10 DC expressing C1Q and STAB are induced. KLRG1 IL10 ILC2 were shown to be induced in AIT in correlation with efficacy. B cells secreting IL-10, IL-35, and TGF-β are induced. Blocking antibodies IgG, IgA, and IgG4 are increased during AIT; whereas inflammatory metabolites, such as eicosanoids, are reduced. There are multiple promising biomarkers for AIT currently being evaluated. A panomic approach is essential to better understand cellular, molecular mechanisms and their correlation with clinical outcomes. Identification of predictive biomarkers of AIT efficacy will hugely impact current practice allowing physicians to select eligible patients that are likely to respond to treatment as well as improve patients' compliance to complete the course of treatment.
过敏性鼻炎是一种由IgE介导的炎症，仍然是一个临床挑战，影响着40%的英国人口，严重程度范围广泛，从鼻腔不适到危及生命的过敏反应。它可以通过药物治疗进行管理，在选定的患者中也可采用变应原免疫疗法（AIT），该疗法具有长期临床疗效，尤其是在过敏高峰期。然而，目前尚无用于评估AIT疗效的明确生物标志物。在此，我们旨在总结在AIT反应中生物标志物识别方面关键的适应性、先天性、体液和代谢进展。疗效机制包括向分泌IFN-γ的T1细胞的免疫偏移，以及已观察到的IL10 cT和T细胞的诱导。由于慢性变应原暴露，AIT后T2细胞会耗竭，并与耗竭标志物PD-1、CTLA-4、TIGIT和LAG3相关。诱导表达C1Q和STAB的IL10 DC。已证明在AIT中诱导产生与疗效相关的KLRG1 IL10 ILC2。诱导分泌IL-10、IL-35和TGF-β的B细胞。AIT期间阻断抗体IgG、IgA和IgG4增加；而炎症代谢产物，如类花生酸，则减少。目前有多种有前景的AIT生物标志物正在评估中。全面的方法对于更好地理解细胞和分子机制及其与临床结果的相关性至关重要。识别AIT疗效的预测性生物标志物将对当前实践产生巨大影响，使医生能够选择可能对治疗有反应的合格患者，并提高患者完成治疗疗程的依从性。
