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豚草皮下和舌下免疫治疗后过敏原特异性 IgA 反应的差异诱导。

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy.

机构信息

National Heart and Lung Institute, Allergy and Clinical Immunology, Imperial College NIHR Biomedical Research Centre, Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom.

Immune Tolerance Network, Bethesda, Md.

出版信息

J Allergy Clin Immunol. 2021 Oct;148(4):1061-1071.e11. doi: 10.1016/j.jaci.2021.03.030. Epub 2021 Apr 2.

Abstract

INTRODUCTION

There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT).

OBJECTIVE

We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial.

METHODS

Nasal fluid and serum were obtained yearly (per-protocol population, n = 84). TGP-specific IgA, IgA, IgG, IgG, and IgE were measured in nasal fluids by ELISA. TGP-specific IgA, IgA, and Phleum pratense (Phl p)1, 2, 4, 5b, 6, 7, 11, and 12 IgE and IgG were measured in sera by ELISA and ImmunoCAP, respectively.

RESULTS

At years 2 and 3, TGP-IgA levels in nasal fluid were elevated in SLIT compared with SCIT (4.2- and 3.0-fold for IgA, 2.0- and 1.8-fold for IgA, respectively; all P < .01). TGP-IgA level in serum was elevated in SLIT compared with SCIT at years 1, 2, and 3 (4.6-, 5.1-, and 4.7-fold, respectively; all P < .001). Serum TGP-IgG level was higher in SCIT compared with SLIT (2.8-fold) at year 2. Serum TGP-IgG level was higher in SCIT compared with SLIT at years 1, 2, and 3 (10.4-, 27.4-, and 5.1-fold, respectively; all P < .01). Serum IgG levels to Phl p1, 2, 5b, and 6 were increased at years 1, 2, and 3 in SCIT and SLIT compared with placebo (Phl p1: 11.8- and 3.9-fold; Phl p2: 31.6- and 4.4-fold; Phl p5b: 135.5- and 5.3-fold; Phl p6: 145.4- and 14.7-fold, respectively, all at year 2 when levels peaked; P < .05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not at year 3 compared with SCIT (2.8-fold; P = .04) and placebo (3.1-fold; P = .02). IgA to TGP and IgE and IgG to TGP components stratified participants according to treatment group and clinical response.

CONCLUSIONS

The observed induction of IgA in SLIT and IgG in SCIT suggest key differences in the mechanisms of action.

摘要

简介

目前还没有舌下免疫疗法(SLIT)和皮下免疫疗法(SCIT)后过敏原特异性免疫球蛋白反应的详细比较。

目的

我们旨在比较 2 年 SCIT 和 SLIT 治疗以及治疗停止 1 年后,在一项双盲、双模拟、安慰剂对照试验中, Timothy 草花粉(TGP)特异性鼻内和全身抗体反应。

方法

每年(按方案人群,n=84)采集鼻液和血清。通过 ELISA 测量鼻液中 TGP 特异性 IgA、IgA、IgG、IgG 和 IgE。通过 ELISA 和 ImmunoCAP 分别测量血清中 TGP 特异性 IgA、IgA 和 Phleum pratense(Phl p)1、2、4、5b、6、7、11 和 12 IgE 和 IgG。

结果

在第 2 年和第 3 年,SLIT 组 TGP-IgA 水平在鼻液中高于 SCIT 组(IgA 为 4.2-和 3.0 倍,IgA 为 2.0-和 1.8 倍;所有 P<0.01)。SLIT 组 TGP-IgA 水平在第 1、2 和 3 年均高于 SCIT 组(分别为 4.6-、5.1-和 4.7 倍;所有 P<0.001)。SCIT 组血清 TGP-IgG 水平高于 SLIT 组(2.8 倍),在第 2 年。SCIT 组血清 TGP-IgG 水平在第 1、2 和 3 年均高于 SLIT 组(分别为 10.4-、27.4-和 5.1 倍;所有 P<0.01)。与安慰剂相比,SCIT 和 SLIT 在第 1、2 和 3 年血清中 Phl p1、2、5b 和 6 的 IgG 水平均升高(Phl p1:11.8-和 3.9 倍;Phl p2:31.6-和 4.4 倍;Phl p5b:135.5-和 5.3 倍;Phl p6:145.4-和 14.7 倍,所有水平在第 2 年达到峰值;P<0.05)。与 SCIT 和安慰剂相比,SLIT 组在第 2 年时 TGP 鼻内 IgE 增加,但第 3 年时无变化(2.8 倍;P=0.04)。TGP 特异性 IgA、IgE 和 IgG 可根据治疗组和临床反应将参与者分层。

结论

SLIT 中观察到的 IgA 诱导和 SCIT 中的 IgG 诱导表明作用机制存在关键差异。

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