Quoc Quang Luu, Cao Thi Bich Tra, Seo Sungbaek, An Beum-Soo, Hwang Dae Youn, Choi Youngwoo, Park Hae-Sim
Department of Oral & Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA.
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Allergy Asthma Immunol Res. 2024 Jul;16(4):353-371. doi: 10.4168/aair.2024.16.4.353.
Patients with non-eosinophilic asthma (NEA) are less responsive to anti-inflammatory drugs and suffer from frequent asthma exacerbations. The pathogenic mechanism of NEA is not fully understood; however, the roles of monocytes and autoimmune mechanisms targeting airway epithelial cell (AEC) antigens have been proposed.
The effects of monocyte extracellular traps (MoETs) on cytokeratin 19 (CK19) production in AECs, as well as the impact of CK19-specific immunoglobulin (Ig) G on neutrophil and monocyte activation, were investigated both and . Sixty asthmatic patients and 15 healthy controls (HCs) were enrolled, and the levels of serum immune complexes containing CK19-specific IgG and neutrophil extracellular trap (NET)-specific IgG were measured using enzyme-linked immunoassay.
MoETs induced CK19 and CK19-specific IgG production. Furthermore, the levels of serum CK19-specific IgG were significantly higher in the NEA group than in the eosinophilic asthma group. Among patients with NEA, asthmatics with high levels of CK19-specific IgG had higher levels of myeloperoxidase and NET-specific IgG than those with low levels of CK19-specific IgG ( = 0.020 and = 0.017; respectively). Moreover, the immune complexes from asthmatics with high CK19-specific IgG enhanced NET formation and reactive oxygen species production (neutrophil activation), which were suppressed by N-acetylcysteine and anti-CD16 antibody treatment.
These findings suggest that circulating CK19 and CK19-specific IgG may contribute to NET formation, leading to airway inflammation and steroid resistance in NEA.
非嗜酸性粒细胞性哮喘（NEA）患者对抗炎药物反应较差，且哮喘频繁发作。NEA的发病机制尚未完全明确；然而，单核细胞以及针对气道上皮细胞（AEC）抗原的自身免疫机制的作用已被提出。
研究了单核细胞胞外陷阱（MoETs）对AECs中细胞角蛋白19（CK19）产生的影响，以及CK19特异性免疫球蛋白（Ig）G对中性粒细胞和单核细胞活化的影响。纳入60例哮喘患者和15例健康对照（HCs），采用酶联免疫吸附测定法检测含CK19特异性IgG和中性粒细胞胞外陷阱（NET）特异性IgG的血清免疫复合物水平。
MoETs诱导CK19和CK19特异性IgG产生。此外，NEA组血清CK19特异性IgG水平显著高于嗜酸性粒细胞性哮喘组。在NEA患者中，CK19特异性IgG水平高的哮喘患者的髓过氧化物酶和NET特异性IgG水平高于CK19特异性IgG水平低的患者（分别为P = 0.020和P = 0.017）。此外，CK19特异性IgG水平高的哮喘患者的免疫复合物增强了NET形成和活性氧产生（中性粒细胞活化），N-乙酰半胱氨酸和抗CD16抗体治疗可抑制这些作用。
这些发现表明，循环中的CK19和CK19特异性IgG可能有助于NET形成，导致NEA患者气道炎症和激素抵抗。
