Huber Sara, Lang Roland, Steiner Markus, Aglas Lorenz, Ferreira Fatima, Wallner Michael, Hawranek Thomas, Gadermaier Gabriele
1Department of Biosciences, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.
2Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria.
Clin Transl Allergy. 2018 Oct 8;8:39. doi: 10.1186/s13601-018-0226-7. eCollection 2018.
The clinical benefit of allergen-specific immunotherapy (AIT) involves induction of blocking antibodies. It is not clear if these antibodies function via steric hindrance alone or a combination of levels, avidities, and epitope specificities, and clinical outcome cannot be predicted. We aim to in-depth characterize serum antibody profiles during birch pollen AIT, investigate therapy-induced antibodies for their capacity to block IgE binding to Bet v 1 and correlate data with clinical outcomes.
Immune responses of five birch pollen allergic patients were monitored during the first year of AIT by nasal provocation tests (NPTs), ImmunoCAP, immunoblots, direct and avidity enzyme-linked immunosorbent assays, mediator release assays, facilitated antigen binding (FAB) assays, and inhibition mediator release assays.
There was no correlation between NPT results and therapy-induced changes in levels (IgE, IgG, IgA, IgM), avidities, or mediator release potency of Bet v 1-specific antibodies. In FAB assays, blocking antibodies initiated upon AIT were shown to prevent formation of Bet v 1-IgE complexes of an indicator serum pool and significantly correlated with clinical readout. Inhibition mediator release assays using patient-specific IgE for passive sensitization revealed therapy-induced blocking capacities with very good correlation to NPT results. Notably, this assay was the only one to detect a non-responder during treatment in this pilot study.
Clinical outcome of AIT depends on induction of blocking antibodies able to prevent the patient's own IgE from allergen binding. Monitoring of clinical efficacy seems to be best achieved using the inhibition mediator release assay, as development of relevant blocking antibodies can be verified in a patient-tailored manner.
变应原特异性免疫疗法（AIT）的临床益处涉及诱导阻断抗体。目前尚不清楚这些抗体是否仅通过空间位阻起作用，还是通过水平、亲和力和表位特异性的组合起作用，并且无法预测临床结果。我们旨在深入表征桦树花粉AIT期间的血清抗体谱，研究治疗诱导的抗体阻断IgE与Bet v 1结合的能力，并将数据与临床结果相关联。
通过鼻激发试验（NPT）、免疫捕获法、免疫印迹法、直接和亲和力酶联免疫吸附测定法、介质释放测定法、促进抗原结合（FAB）测定法和抑制介质释放测定法，在AIT的第一年监测5名桦树花粉过敏患者的免疫反应。
NPT结果与Bet v 1特异性抗体的水平（IgE、IgG、IgA、IgM）、亲和力或介质释放能力的治疗诱导变化之间没有相关性。在FAB测定中，AIT开始时产生的阻断抗体可阻止指示血清池的Bet v 1-IgE复合物形成，并且与临床读数显著相关。使用患者特异性IgE进行被动致敏的抑制介质释放测定显示治疗诱导的阻断能力与NPT结果具有很好的相关性。值得注意的是，在这项初步研究中，该测定是唯一能检测出治疗期间无反应者的方法。
AIT的临床结果取决于诱导能够阻止患者自身IgE与变应原结合的阻断抗体。使用抑制介质释放测定似乎最能监测临床疗效，因为可以以患者定制的方式验证相关阻断抗体的产生。
