血清烟曲霉特异性 IgE、IgG 和 IgG4 免疫球蛋白在侵袭性肺曲霉病中的评估：一项前瞻性队列研究。

Serum Aspergillus-specific IgE, IgG and IgG4 immunoglobulins assessment in the work-up of invasive pulmonary aspergillosis: a prospective cohort study.

机构信息

Respiratory Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy -

Unit of Pulmonology, Department of Medical Sciences and Infectious Diseases, IRCCS Policlinico San Matteo University Hospital, Pavia, Italy -

出版信息

Minerva Med. 2023 Aug;114(4):433-443. doi: 10.23736/S0026-4806.22.08245-3. Epub 2022 Jul 29.

DOI:10.23736/S0026-4806.22.08245-3

PMID:35904372

Abstract

BACKGROUND

Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG4, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy).

METHODS

We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG4 specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patients.

RESULTS

Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG4 showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM.

CONCLUSIONS

In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

摘要

背景

从支气管肺泡灌洗液（BAL）中分离出曲霉菌或组织活检，并检测到高水平的曲霉菌半乳甘露聚糖（GM）通常被认为是诊断侵袭性肺曲霉病（IPA）的标准。然而，曲霉菌感染会引起细胞和体液免疫反应，表现为特异性免疫球蛋白的产生，这些免疫球蛋白可以在血清中很容易地检测到，并能准确地测量。本研究假设曲霉菌特异性 IgE、IgG，包括 IgG4，检测可以作为疑似曲霉菌相关肺部疾病患者的快速初步筛选工具，以帮助识别需要更具侵袭性程序（支气管镜检查、活检）的患者。

方法

我们前瞻性地储存了 2010 年 1 月 1 日至 2021 年 7 月 31 日期间因疑似 IPA 入院的 447 例患者的血清标本。对每个样本均测定血清总 IgE 和血清 IgE、IgG 和 Aspergillus fumigatus 和 Aspergillus niger 的 IgG4特异性。此外，所有患者均进行支气管镜检查以进行微生物培养和曲霉半乳甘露聚糖（GM）抗原检测。

结果

通过检测 BAL 培养阳性的曲霉菌和/或 GM 阳性诊断为 IPA 的患者，其血清中特异性曲霉菌 fumigatus 和 Aspergillus niger 免疫球蛋白水平更高。血清特异性 Aspergillus fumigatus IgG 截值为 22.6mgA/L 时，对 IPA 的预测具有最高的敏感性，尽管相当中等（AUC 0.62）。然而，同时存在低于 Aspergillus IgE、IgG 和 IgG4截值的情况，对 BAL 培养阳性和 GM 阳性均具有大于 90%的阴性预测值。