Synchronous immune alterations mirror clinical response during allergen immunotherapy.
Synchronous immune alterations mirror clinical response during allergen immunotherapy.
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DOI：
10.1016/j.jaci.2017.09.041
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Durham SR
中科院分区：
文献类型：
--
作者：
Renand A;Shamji MH;Harris KM;Qin T;Wambre E;Scadding GW;Wurtzen PA;Till SJ;Togias A;Nepom GT;Kwok WW;Durham SR
三年的舌下或皮下过敏原免疫治疗已被证明是有效的，并诱导长期耐受性。GRASS*试验表明，通过两种途径治疗2年可有效抑制对鼻腔过敏原的反应，尽管停药1年后抑制作用不足。在GRASS试验中检查两年内舌下和皮下免疫治疗和治疗停止后一年免疫变化的时间过程。我们进行了多模式免疫监测，以评估过敏原特异性CD4 T细胞的特性，同时分析鼻腔过敏原暴露诱导的局部粘膜细胞因子反应和体液免疫反应，包括ige依赖的嗜碱性粒细胞激活和测量血清对过敏原ige与B细胞结合的抑制活性（ige促进过敏原结合）。在2年的过敏原脱敏期间，所有这三个不同的免疫反应臂都显示出显著和协调的改变，随后在3年逆转，反映了缺乏持久的免疫效应。尽管HLA II类四聚体分析测定的外周血中抗原特异性Th2细胞的频率与临床结果最接近，但停药一年后，ige抗体依赖的功能测定仍部分受到抑制。两年的过敏原免疫治疗是有效的，但不足以长期耐受。过敏原特异性Th2细胞与短暂的临床结果密切相关，很可能是过敏性免疫的T细胞“驱动因素”的复发取消了持久耐受性的潜力。另一方面，停药一年后持续存在ige阻断抗体可能是促耐受性机制的早期指标。
Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS* trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation. We performed multi-modal immunomonitoring to assess allergen-specific CD4 T cell properties, in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-Facilitated Allergen Binding). All three of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunological effect. Whereas frequencies of antigen-specific Th2 cells in peripheral blood determined by HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE-antibody dependent functional assays remained partially inhibited one year following discontinuation. Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific Th2 cells most closely paralleled the transient clinical outcome and it is likely that recurrence of the T cell ‘drivers’ of allergic immunity abrogated the potential for durable tolerance. On the other hand, persistence of IgE-blocking antibody one year after discontinuation may be an early indicator of a pro-tolerogenic mechanism.
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影响因子：
14.2
作者：
James, Louisa K.;Shamji, Mohamed H.;Durham, Stephen R.
通讯作者：
Durham, Stephen R.
影响因子：
14.2
作者：
Francis, James N.;James, Louisa K.;Till, Stephen J.
通讯作者：
Till, Stephen J.
影响因子：
5.4
作者：
Jutel, M;Akdis, M;Akdis, CA
通讯作者：
Akdis, CA
影响因子：
2.8
作者：
Fanta, C;Bohle, B;Ebner, C
通讯作者：
Ebner, C
影响因子：
14.2
作者：
Francis, JN;Till, SJ;Durham, SR
通讯作者：
Durham, SR