Non-allergic Hypersensitivity Reactions to Immunoglobulin Preparations in Antibody Deficiencies: What Role for Anti-IgA IgG and Complement Activation?

IF 8.4 2区 医学 Q1 ALLERGY Clinical Reviews in Allergy & Immunology Pub Date : 2024-10-22 DOI:10.1007/s12016-024-09007-0
Aurore Collet, Diane Pelletier de Chambure, Emmanuelle Moitrot, Gaëlle Breyne, Floriane Mirgot, Stéphanie Rogeau, Mathieu Tronchon, Amélie Nicolas, Sébastien Sanges, Sarah Stabler, Emmanuel Ledoult, Louis Terriou, David Launay, Eric Hachulla, Myriam Labalette, Sylvain Dubucquoi, Guillaume Lefèvre
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Abstract

The presence of IgG anti-IgA in the serum of primary immunodeficiency (PID) patients has long been considered responsible for hypersensitivity (HS) to immunoglobulin preparations (IgPs), but this link is increasingly being questioned. The aim of this work was to describe the prevalence of IgG anti-IgA and its association with HS, and to explore a new pathophysiological hypothesis involving the complement system. We measured IgG anti-IgA, using a standardised commercial technique, in controls and PID patients, and compared our results to a systematic literature review. We measured complement activation in PID patients before and after IgP infusion, and in vitro after incubation of IgP with serum from controls and PID patients. IgG anti-IgA was detected in 6% (n = 2/32) of PID patients, 30% (n = 3/10) of selective IgA deficiency patients and 2% (n = 1/46) of healthy controls. In the literature and our study, 38 PID patients had IgG anti-IgA and HS to IgPs and 9 had IgG anti-IgA but good tolerance to IgPs. In our patients, we observed a constant complement activation after IgP infusion compared to baseline. In vitro, IgP induced significant complement activation with all sera from tested individuals. IgA immunisation is not rare in PID, higher in selective IgA deficiency, but may also occur in healthy controls. Our results question the clinical relevance and pathophysiological implication of IgG anti-IgA in the context of HS with IgPs. Complement activation-related pseudoallergy could explain the clinical characteristics and natural history of HS symptoms.

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抗体缺乏症患者对免疫球蛋白制剂的非过敏性超敏反应:抗IgA IgG和补体激活的作用是什么?
长期以来,人们一直认为原发性免疫缺陷(PID)患者血清中存在的 IgG 抗 IgA 是造成对免疫球蛋白制剂(IgPs)过敏(HS)的原因,但这种联系正日益受到质疑。这项研究的目的是描述 IgG 抗 IgA 的患病率及其与 HS 的关系,并探索一种涉及补体系统的新病理生理学假说。我们使用标准化商业技术测量了对照组和 PID 患者的 IgG 抗 IgA,并将结果与系统性文献综述进行了比较。我们测量了 PID 患者输注 IgP 前后的补体激活情况,以及 IgP 与对照组和 PID 患者血清孵育后的体外补体激活情况。在 6% 的 PID 患者(n = 2/32)、30% 的选择性 IgA 缺乏患者(n = 3/10)和 2% 的健康对照组(n = 1/46)中检测到 IgG 抗 IgA。在文献和我们的研究中,38 名 PID 患者具有 IgG 抗 IgA 和对 IgPs 的 HS,9 名患者具有 IgG 抗 IgA,但对 IgPs 有良好的耐受性。在我们的患者中,与基线相比,我们观察到输注 IgP 后补体持续激活。在体外,所有受试者的血清中,IgP 都能诱导明显的补体激活。IgA 免疫在 PID 中并不罕见,在选择性 IgA 缺乏症中更高,但也可能发生在健康对照组中。我们的研究结果对 IgG 抗 IgA 与 IgPs HS 的临床相关性和病理生理学意义提出了质疑。补体活化相关假过敏可解释 HS 症状的临床特征和自然病史。
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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
期刊最新文献
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