Dept of Medicine, Firestone Institute of Respiratory Health and St Joseph's Healthcare, McMaster University, Hamilton, ON, Canada.
Brittany Salter and Nan Zhao contributed equally.
Eur Respir J. 2022 Dec 1;60(6). doi: 10.1183/13993003.00442-2022. Print 2022 Dec.
Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma. Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO) and nuclear/extranuclear antigens (antinuclear antibodies (ANAs)) have been reported. Our objective was to describe the prevalence and clinical characteristics of asthmatic patients with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity.
We analysed anti-EPX, anti-MARCO and ANAs in 218 sputum samples collected prospectively from 148 asthmatic patients, and evaluated their association with lung function parameters, blood/airway inflammation, severity indices and exacerbations. Additionally, 107 of these patients consented to fill out an autoimmune checklist to determine personal/family history of systemic autoimmune disease and symptoms.
Out of the 148 patients, 59 (40%) were anti-EPX IgG, 53 (36%) were anti-MARCO IgG and 64 out of 129 (50%) had ≥2 nuclear/extranuclear autoreactivities. A composite airway autoreactivity score (CAAS) demonstrated that 82 patients (55%) had ≥2 airway autoreactivities (considered as CAAS). Increased airway eosinophil degranulation (OR 15.1, 95% CI 1.1-199.4), increased blood leukocytes (OR 3.5, 95% CI 1.3-10.1) and reduced blood lymphocytes (OR 0.19, 95% CI 0.04-0.84) predicted CAAS. A third of CAAS patients reported an exacerbation, associated with increased anti-EPX and/or anti-MARCO IgG (p<0.05). While no association was found between family history or personal diagnosis of autoimmune disease, 30% of CAAS asthmatic patients reported sicca symptoms (p=0.02). Current anti-inflammatory (inhaled/oral corticosteroids and/or adjunct anti-interleukin-5 biologics) treatment does not attenuate airway autoantibodies, irrespective of eosinophil suppression.
We report 55% of moderate-severe asthmatic patients to have airway autoreactivity that persists despite anti-inflammatory treatment and is associated with exacerbations.
局部气道自身免疫反应可能导致重度哮喘患者对类固醇产生依赖性和持续的嗜酸性粒细胞增多症。已经报道了针对颗粒蛋白（如嗜酸粒细胞过氧化物酶 (EPX)、巨噬细胞清道夫受体胶原蛋白结构域 (MARCO) 和核/核外抗原（抗核抗体 (ANA)）的自身 IgG 抗体。我们的目的是描述气道自身反应性哮喘患者的患病率和临床特征，并评估是否可以从自身反应性的临床病史中预测到这种情况。
我们分析了前瞻性收集的 148 例哮喘患者的 218 份痰样本中的抗 EPX、抗 MARCO 和 ANA，并评估了它们与肺功能参数、血液/气道炎症、严重程度指数和加重的关系。此外，这些患者中有 107 例同意填写自身免疫检查表，以确定个人/家族自身免疫性疾病史和症状。
在 148 例患者中，59 例（40%）为抗 EPX IgG，53 例（36%）为抗 MARCO IgG，129 例中有 64 例（50%）有≥2 种核/核外自身反应性。气道自身反应复合评分（CAAS）显示，82 例患者（55%）有≥2 种气道自身反应性（被认为是 CAAS）。气道嗜酸性粒细胞脱颗粒增加（OR 15.1，95%CI 1.1-199.4）、血液白细胞增加（OR 3.5，95%CI 1.3-10.1）和血液淋巴细胞减少（OR 0.19，95%CI 0.04-0.84）预测 CAAS。三分之一的 CAAS 患者报告了加重，与抗 EPX 和/或抗 MARCO IgG 的增加有关（p<0.05）。虽然家族史或自身免疫性疾病的个人诊断之间没有发现关联，但 30%的 CAAS 哮喘患者报告有干燥症状（p=0.02）。当前的抗炎（吸入/口服皮质类固醇和/或辅助抗白细胞介素-5 生物制剂）治疗并不能减轻气道自身抗体，无论是否抑制嗜酸性粒细胞。
我们报告称，55%的中重度哮喘患者存在气道自身反应性，即使在抗炎治疗下仍持续存在，并与加重有关。
