鼻过敏原中和 IgG 抗体可阻断 IgE 介导的反应：皮下草花粉免疫治疗的新型生物标志物。

Nasal allergen-neutralizing IgG antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy.

机构信息

Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, National Heart and Lung Institute, Inflammation Repair and Development, Imperial College, London, United Kingdom.

Allergy and Clinical Immunology, Immunomodulation and Tolerance Group, National Heart and Lung Institute, Inflammation Repair and Development, Imperial College, London, United Kingdom; Department of Pulmonology, STZ Centre of Excellence for Asthma & COPD, Franciscus group, Rotterdam, United Kingdom.

出版信息

J Allergy Clin Immunol. 2019 Mar;143(3):1067-1076. doi: 10.1016/j.jaci.2018.09.039. Epub 2018 Nov 14.

DOI:10.1016/j.jaci.2018.09.039

PMID:30445057

Abstract

BACKGROUND

Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells.

OBJECTIVE

We sought to determine whether SCIT induces nasal allergen-specific IgG antibodies with inhibitory activity that correlates closely with clinical response.

METHODS

In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects. Nasal and serum IgE and IgG levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10 regulatory B cells were quantified in peripheral blood by using flow cytometry.

RESULTS

Nasal and serum Phl p 1- and Phl p 5-specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P < .001) and SCIT-treated patients (nasal, P < .001; serum Phl p 5, P = .073). Nasal IgG levels were increased in the SCIT group compared to those in the SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P < .01). The magnitude of the inhibitory activity was 93% (P < .001) in nasal fluid compared to 66% (P < .001) in serum and was reversed after depletion of IgG. Both nasal fluid (r = -0.69, P = .0005) and serum (r = -0.552, P = .0095) blocking activity correlated with global symptom improvement. IL-10 regulatory B cells were increased in season compared to out of season in the SCIT group (P < .01).

CONCLUSION

For the first time, we show that nasal IgG-associated inhibitory activity correlates closely with the clinical response to allergen immunotherapy in patients with allergic rhinitis with or without asthma.

摘要

背景

草花粉皮下免疫疗法（SCIT）与诱导血清 IgG 相关抑制性抗体有关，这些抗体可防止 IgE 促进过敏原与 B 细胞结合。

目的

我们旨在确定 SCIT 是否诱导具有密切临床反应相关性的鼻过敏原特异性 IgG 抗体，这些抗体具有抑制活性。

方法

在一项横断面对照研究中，在花粉季节期间，从 10 名接受 SCIT 治疗的患者、13 名未经治疗的过敏患者（季节性过敏性鼻炎 [SAR]）和 12 名非过敏对照受试者中采集鼻液和血清。通过使用 Immuno Solid Allergen Chip 微阵列测量 Phleum pratense 成分的鼻和血清 IgE 和 IgG 水平。通过 IgE 促进的过敏原结合测定法测量抑制活性。通过流式细胞术定量外周血中的 IL-10 调节性 B 细胞。

结果

与非过敏对照受试者（均 P<.001）和接受 SCIT 治疗的患者（鼻，P<.001；血清 Phl p 5，P=.073）相比，SAR 患者的鼻和血清中 Phl p 1 和 Phl p 5 特异性 IgE 水平均升高。与 SAR 组相比，SCIT 组在花粉季节期间的鼻和血清 IgG 水平升高（均 P<.001），而在非花粉季节期间则降低。与 SAR 组相比，SCIT 组的鼻液和血清中与 IgG 相关的抑制活性显著增加（均 P<.01）。鼻液中的抑制活性为 93%（P<.001），而血清中的抑制活性为 66%（P<.001），且在 IgG 耗尽后逆转。鼻液（r=-0.69，P=.0005）和血清（r=-0.552，P=.0095）阻断活性均与整体症状改善相关。与非花粉季节相比，SCIT 组在花粉季节中 IL-10 调节性 B 细胞增加（P<.01）。