气道自身抗体是哮喘严重程度的决定因素
2022/07/19
摘要
背景：局部气道自身免疫反应可能导致重症哮喘（SA）患者激素依赖和持续性嗜酸性粒细胞增多。自身抗体颗粒蛋白IgG，例如嗜酸性粒细胞过氧化物酶（EPX）、具有胶原结构的巨噬细胞清道夫受体（MACO）和核/核外抗原（ANA）已被报道。
目的：描述具有气道自身免疫反应的哮喘患者的患病率和临床特征，并评估其是否可以从自身免疫的临床病史中预测。
方法：我们分析了从148例哮喘患者前瞻性采集的218份痰样本中的抗-EPX、抗-MARCO和抗-ANA，并评估其与肺功能、血液/气道炎症、严重程度指数和急性发作的关系。此外，107名患者同意填写自身免疫检查表，以确定系统性自身免疫疾病的个人/家族病史和症状。
结果：148例患者中，59例（40%）抗EPX-IgG阳性，53例（36%）抗MARCO-IgG阳性，65例（50%）≥2核/核外自免疫反应。综合气道自身反应性评分（CAAS）显示82名患者（55%）患有哮喘≥2气道自身反应性（视为CAAS+）。气道嗜酸性粒细胞脱颗粒增加（OR:15.1；CI:1.1-199.4）、血白细胞（OR:3.5；CI:1.3-10.1）、血淋巴细胞减少（OR:0.19；CI:0.04-0.84）预测CAAS+。三分之一的CAAS+患者报告病情加重，与抗EPX和/或抗MARCO IgG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相关性，但30%的CAAS+哮喘患者报告了Sicca症状（p=0.02）。目前的抗炎（吸入/口服皮质类固醇和/或辅助抗IL-5生物制剂）治疗不会减弱气道自身抗体，且与嗜酸性粒细胞抑制无关。
结论：我们报告55%的中重度哮喘患者尽管进行了抗炎治疗，但气道自身免疫反应仍持续存在，并与病情加重有关。
Airway autoantibodies are determinants of asthma severity
Brittany Salter, Nan Zhao, Kiho Son, Nadia Suray Tan, Anna Dvorkin-Gheva, Katherine Radford, Nicola LaVigne, Chynna Huang, Melanie Kjarsgaard, Quan-Zhen Li, Konstantinos Tselios, Hui Fang Lim MD, Nader Khalidi, Parameswaran Nair, Manali Mukherjee
Abstract
Background：Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma (SA). Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO), and nuclear/extra-nuclear antigens (ANAs) have been reported.
Objective：To describe the prevalence and clinical characteristics of asthmatics with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity.
Methods：We analysed anti-EPX, anti-MARCO, and ANAs in 218 sputum samples collected prospectively from 148 asthmatics, 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.
Results：Out of the 148 patients, 59 (40%) were anti-EPX IgG positive, 53 (36%) were anti-MARCO IgG positive, and 65 (50%) had ≥2 nuclear/extra-nuclear 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; CI:1·1-199·4), blood leukocytes (OR:3·5; CI:1·3-10·1), reduced blood lymphocytes (OR:0·19; 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+ asthmatics reported Sicca symptoms (p=0·02). Current anti-inflammatory (inhaled/oral corticosteroids and/or adjunct anti-IL-5 biologics) treatment does not attenuate airway autoantibodies, irrespective of eosinophil suppression.
Conclusion：We report 55% of moderate-to-severe asthmatics to have airway autoreactivity that persists despite anti-inflammatory treatment, and is associated with exacerbations.
背景：局部气道自身免疫反应可能导致重症哮喘（SA）患者激素依赖和持续性嗜酸性粒细胞增多。自身抗体颗粒蛋白IgG，例如嗜酸性粒细胞过氧化物酶（EPX）、具有胶原结构的巨噬细胞清道夫受体（MACO）和核/核外抗原（ANA）已被报道。
目的：描述具有气道自身免疫反应的哮喘患者的患病率和临床特征，并评估其是否可以从自身免疫的临床病史中预测。
方法：我们分析了从148例哮喘患者前瞻性采集的218份痰样本中的抗-EPX、抗-MARCO和抗-ANA，并评估其与肺功能、血液/气道炎症、严重程度指数和急性发作的关系。此外，107名患者同意填写自身免疫检查表，以确定系统性自身免疫疾病的个人/家族病史和症状。
结果：148例患者中，59例（40%）抗EPX-IgG阳性，53例（36%）抗MARCO-IgG阳性，65例（50%）≥2核/核外自免疫反应。综合气道自身反应性评分（CAAS）显示82名患者（55%）患有哮喘≥2气道自身反应性（视为CAAS+）。气道嗜酸性粒细胞脱颗粒增加（OR:15.1；CI:1.1-199.4）、血白细胞（OR:3.5；CI:1.3-10.1）、血淋巴细胞减少（OR:0.19；CI:0.04-0.84）预测CAAS+。三分之一的CAAS+患者报告病情加重，与抗EPX和/或抗MARCO IgG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相关性，但30%的CAAS+哮喘患者报告了Sicca症状（p=0.02）。目前的抗炎（吸入/口服皮质类固醇和/或辅助抗IL-5生物制剂）治疗不会减弱气道自身抗体，且与嗜酸性粒细胞抑制无关。
结论：我们报告55%的中重度哮喘患者尽管进行了抗炎治疗，但气道自身免疫反应仍持续存在，并与病情加重有关。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Eur Respir J. 2022 Jul 1;2200442. doi: 10.1183/13993003.00442-2022.)
(Eur Respir J. 2022 Jul 1;2200442. doi: 10.1183/13993003.00442-2022.)
Airway autoantibodies are determinants of asthma severity
Brittany Salter, Nan Zhao, Kiho Son, Nadia Suray Tan, Anna Dvorkin-Gheva, Katherine Radford, Nicola LaVigne, Chynna Huang, Melanie Kjarsgaard, Quan-Zhen Li, Konstantinos Tselios, Hui Fang Lim MD, Nader Khalidi, Parameswaran Nair, Manali Mukherjee
Abstract
Background：Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma (SA). Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO), and nuclear/extra-nuclear antigens (ANAs) have been reported.
Objective：To describe the prevalence and clinical characteristics of asthmatics with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity.
Methods：We analysed anti-EPX, anti-MARCO, and ANAs in 218 sputum samples collected prospectively from 148 asthmatics, 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.
Results：Out of the 148 patients, 59 (40%) were anti-EPX IgG positive, 53 (36%) were anti-MARCO IgG positive, and 65 (50%) had ≥2 nuclear/extra-nuclear 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; CI:1·1-199·4), blood leukocytes (OR:3·5; CI:1·3-10·1), reduced blood lymphocytes (OR:0·19; 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+ asthmatics reported Sicca symptoms (p=0·02). Current anti-inflammatory (inhaled/oral corticosteroids and/or adjunct anti-IL-5 biologics) treatment does not attenuate airway autoantibodies, irrespective of eosinophil suppression.
Conclusion：We report 55% of moderate-to-severe asthmatics to have airway autoreactivity that persists despite anti-inflammatory treatment, and is associated with exacerbations.
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