花粉过敏儿童中环孢素 IgE：被忽视的泛过敏原的流行病学、临床和诊断相关性。

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

机构信息

Charité-Universitätsmedizin Berlin, a corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Germany; Institute of Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany.

出版信息

J Allergy Clin Immunol. 2024 Jun;153(6):1586-1596.e2. doi: 10.1016/j.jaci.2024.01.030. Epub 2024 Mar 19.

DOI:10.1016/j.jaci.2024.01.030

PMID:38513837

Abstract

BACKGROUND

Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice.

OBJECTIVE

We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities.

METHODS

We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7.

RESULTS

IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%).

CONCLUSIONS

IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

摘要

背景

亲环素是无处不在的泛过敏原，其在流行病学、诊断和临床方面的相关性在很大程度上尚不清楚，而且在常规过敏实践中很少检查其致敏情况。

目的

我们研究了亲环素在季节性过敏性鼻炎及其合并症中的流行病学、诊断和临床相关性。

方法

我们对来自儿科泛过敏原（PAN-PED）队列的 1263 例季节性过敏性鼻炎患儿中的 253 例（25%）进行了随机抽样，并对其疾病表型进行了特征描述。在对桦树花粉提取物过敏但缺乏对 Bet v 1/2/4 的 IgE（74/1263）或对 Bet v 1 血清 IgE 水平最高的患者（26/1263）中进行了致敏流行率、相关性和过敏原提取物抑制的巢式研究；以及在对各种提取物（豚草、艾蒿、漆树、车前草和悬铃木）过敏但对各自主要过敏原蛋白、丝状蛋白和钙调蛋白无反应的患者中进行了这些研究。使用重组 Bet v 7 检测亲环素 IgE，并使用相同的 rBet v 7 进行提取物抑制试验。

结果

在 253 例患者中，有 43 例（17%）检测到 rBet v 7 的 IgE。在单变量分析中，它与哮喘（P <.028）和口腔过敏综合征（P <.017）相关，但在调整了丝状蛋白（Phl p 12）、PR-10s（Bet v 1）和脂质转移蛋白（Pru p 3）的 IgE 后，多变量分析中没有相关性。rBet v 7 的 IgE 也在对桦树花粉提取物无法解释的过敏患者中高度流行（74/74，63%）。在对豚草、艾蒿、漆树、车前草和悬铃木花粉无法解释的过敏患者中，这些提取物的 IgE 水平与 rBet v 7 的 IgE 水平相关，rBet v 7 也显著抑制了这些提取物（抑制范围 45%-74%）。