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从接受尘螨免疫治疗的患者体内制备的变应原特异性免疫球蛋白G、F(ab')和Fab抗体的阻断功能

Blocking function of allergen-specific immunoglobulin G, F(ab'), and Fab antibodies prepared from patients undergoing Dermatophagoides pteronyssinus immunotherapy.

作者信息

Zhang Huan, Xian Mo, Shi Xu, Luo Tian, Su Qiujuan, Li Jing, Feng Mulin

机构信息

Huizhou Central People's Hospital, Huizhou, Guangdong, People's Republic of China.

Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

出版信息

Ann Allergy Asthma Immunol. 2022 Jun;128(6):689-696. doi: 10.1016/j.anai.2022.03.031. Epub 2022 Apr 8.

Abstract

BACKGROUND

The blocking function of allergen-specific F(ab') [sF(ab')] and Fab (sFab) fragment antibodies prepared from allergen immunotherapy-induced specific immunoglobulin G (sIgG) has not been fully investigated.

OBJECTIVE

To investigate the inhibitory function of sIgG, sF(ab'), and sFab antibodies in patients undergoing Dermatophagoides pteronyssinus (Der-p) subcutaneous immunotherapy (SCIT).

METHODS

This study involved 10 subjects (aged 18-42 years) with house dust mite allergic rhinitis or asthma who received a 156-week course of Der-p SCIT. Total IgG levels were purified from the serum of the participants at weeks 0 and 156 by protein A affinity chromatography. Der-p sIgG was purified by affinity chromatography with Der-p as a ligand at week 156. The sF(ab') and sFab antibodies were prepared from Der-p sIgG by treatment with pepsin and papain, respectively. Furthermore, IgE-facilitated allergen binding assay, basophil activation inhibition test, and cytokine release inhibition assay were used to assess the inhibitory function of Der-p sIgG, sF(ab'), and sFab antibodies.

RESULTS

We found that the Der-p sIgG, sF(ab'), and sFab antibodies markedly blocked Der-p-allergen sIgE complex binding to B cells, inhibited basophil activation, and markedly reduced the production of interleukin (IL)-5, IL-13, IL-17, and tumor necrosis factor-α by peripheral blood mononuclear cells.

CONCLUSION

SCIT-induced Der-p sIgG, sF(ab'), and sFab antibodies may block the formation of Der-p-sIgE complexes and may serve as a potential allergen-targeted biologics candidate for the treatment of allergic asthma.

CLINICAL TRIAL REGISTRATION

This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-15006207, https://www.chictr.org.cn/enindex.aspx).

摘要

背景

从变应原免疫疗法诱导产生的特异性免疫球蛋白G(sIgG)制备的变应原特异性F(ab')[sF(ab')]和Fab(sFab)片段抗体的阻断功能尚未得到充分研究。

目的

研究sIgG、sF(ab')和sFab抗体对接受尘螨皮下免疫疗法(SCIT)患者的抑制功能。

方法

本研究纳入10名年龄在18至42岁之间的屋尘螨过敏性鼻炎或哮喘患者,接受为期156周的尘螨皮下免疫疗法。在第0周和第156周通过蛋白A亲和层析从参与者血清中纯化总IgG水平。在第156周通过以尘螨为配体的亲和层析纯化尘螨sIgG。分别用胃蛋白酶和木瓜蛋白酶处理尘螨sIgG制备sF(ab')和sFab抗体。此外,采用IgE促进的变应原结合试验、嗜碱性粒细胞活化抑制试验和细胞因子释放抑制试验评估尘螨sIgG、sF(ab')和sFab抗体的抑制功能。

结果

我们发现尘螨sIgG、sF(ab')和sFab抗体显著阻断尘螨变应原sIgE复合物与B细胞的结合,抑制嗜碱性粒细胞活化,并显著降低外周血单个核细胞产生白细胞介素(IL)-5、IL-13、IL-17和肿瘤坏死因子-α。

结论

皮下免疫疗法诱导产生的尘螨sIgG,sF(ab')和sFab抗体可能阻断尘螨-sIgE复合物的形成,并可能成为治疗过敏性哮喘的潜在变应原靶向生物制剂候选物。

临床试验注册

本研究经广州医科大学附属第一医院伦理委员会批准,并在中国临床试验注册中心注册(ChiCTR-OOC-15006207,https://www.chictr.org.cn/enindex.aspx)。

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