A microarray-based IgE-molecular mimicry index (IgE-MMI): A biomarker for disease severity, clinical phenotypes, and therapeutic response in atopic dermatitis?

IF 12.6 1区医学 Q1 ALLERGY

Allergy Pub Date : 2024-11-04 DOI:10.1111/all.16377

Enrico Scala, Stefania Madonna, Damiano Abeni, Lorenzo Cecchi, Barbara Cocuroccia, Anna Dattolo, Gaia Moretta, Alessia Provini, Filomena Russo, Donatella Sordi, Sabatino Pallotta, Marco Galluzzo, Marina Talamonti, Valeria Villella, Mauro Giani, Elisabetta Caprini, Cristina Albanesi, Danilo Villalta, Riccardo Asero, Paolo Maria Matricardi

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Abstract

Background

The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self-proteins has been extensively studied, IgE responses induced by human-homologous exogenous molecular allergens (HEMAs) remains less understood.

Aim

To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.

Methods

We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer-ALEX-2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an ‘IgE molecular-mimicry index’ (IgE-MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE-MMI and AD, its severity, and response to dupilumab.

Results

IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non-HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE-MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3–11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4–37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9–15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7–302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02–0.8) and NPC-2 from dust mites (OR: 0.1, 95% CI: 0.01–0.9).

Conclusion

IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE-MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab.

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基于芯片的 IgE 分子模拟指数（IgE-MMI）：特应性皮炎疾病严重程度、临床表型和治疗反应的生物标记？

背景：自身免疫 IgE 反应在特应性皮炎（AD）中的作用备受争议。虽然针对自身蛋白的 IgE 已被广泛研究，但由人类同源外源性分子过敏原（HEMAs）诱导的 IgE 反应仍鲜为人知。目的：研究针对 HEMAs 的 IgE 抗体反应是否与 AD 及其严重程度以及对杜匹单抗的反应有关：我们招募了 3325 名有过敏性疾病史的参与者，其中包括 577 名（17.3%）确诊为 AD 患者。使用 IgE 微阵列（Allergy Explorer-ALEX-2®，MADX，维也纳）测量了血清中针对 183 种外源性过敏原分子的 IgE 抗体。根据国际分类标准，我们按照注意力缺失症的严重程度和临床表型对参与者进行了分层。我们为每位患者制定了一个 "IgE 分子模拟指数"（IgE-MMI），该指数是通过对精氨酸激酶、烯醇化酶 (ENO)、环嗜蛋白 (CYP)、脂钙蛋白和 MnSOD 这五种 HEMA 蛋白家族的 IgE 反应性计算得出的。采用逻辑回归评估了HEMA或IgE-MMI的IgE与AD、其严重程度以及对dupilumab的反应之间的关联：结果：与其他患者群体相比，严重AD患者对大多数HEMAs（32/48，67%），但对一小部分非HEMAs（3/135，2.2%）的IgE过敏现象明显更常见。在 295/2748 例（10.7%）无 AD 的过敏症患者中，IgE-MMI 呈阳性；在缓解型、中度或重度 AD 患者中，IgE-MMI 呈阳性的患者分别为 58/283（20%）、52/134（39%）和 86/160（54%）。它与特定表型密切相关，如屈曲性皮炎（OR：8.4，95% CI：6.3-11.2）、头颈部皮炎（OR：16.5，95% CI：7.4-37.2）和全身湿疹（OR：8.6，95% CI：4.9-15.6）。对杜匹鲁单抗的不良反应与ENO的IgE抗体有关（OR：22.7，95% CI：1.7-302.9），但与MnSOD的IgE抗体（OR：0.1，95% CI：0.02-0.8）和尘螨的NPC-2的IgE抗体（OR：0.1，95% CI：0.01-0.9）成反比：IgE 微阵列有助于广泛评估过敏患者对 HEMAs 的 IgE 反应。对 HEMAs 的 IgE 反应性和 IgE-MMI 阳性可作为严重 AD、其临床表型和对杜匹单抗反应的有价值的生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.