Center for Vaccines and Immunology, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
Pediatrics, Division of Pediatric Pulmonology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
BMJ Open Respir Res. 2021 Mar;8(1). doi: 10.1136/bmjresp-2020-000842.
Although asthma is the most commonly diagnosed respiratory disease, its pathogenesis is complex, involving both genetic and environmental factors. A role for the respiratory microbiome in modifying asthma severity has been recently recognised. Airway colonisation by has previously been associated with multiple chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and severe asthma (SA). Decreased incidence of pneumonia in HIV-infected individuals and reduced severity of COPD is associated with naturally occurring antibody responses to the antigen, Kexin (KEX1).
104 paediatric patients were screened for KEX1 IgG reciprocal end point titre (RET), including 51 with SA, 20 with mild/moderate asthma, 20 non-asthma and 13 with cystic fibrosis (CF) in a cross-sectional study.
Patients with SA had significantly reduced KEX1 titres compared with patients with mild/moderate asthma (p=0.018) and CF (p=0.003). A binary KEX1 RET indicator was determined at a threshold of KEX1 RET=1000. Patients with SA had 4.40 (95% CI 1.28 to 13.25, p=0.014) and 17.92 (95% CI 4.15 to 66.62, p<0.001) times the odds of falling below that threshold compared with mild/moderate asthma and patients with CF, respectively. Moreover, KEX1 IgG RET did not correlate with tetanus toxoid IgG (r=0.21, p=0.82) or total IgE (r=0.03, p=0.76), indicating findings are specific to antibody responses to KEX1.
Paediatric patients with SA may be at higher risk for chronic infections and asthma symptom exacerbation due to reduced levels of protective antibodies. Plasma KEX1 IgG titre may be a useful parameter in determining the clinical course of treatment for paediatric patients with asthma.
虽然哮喘是最常见的诊断性呼吸道疾病,但它的发病机制很复杂,涉及遗传和环境因素。最近人们认识到呼吸微生物组在改变哮喘严重程度方面的作用。以前, 已经与多种慢性肺部疾病有关,包括慢性阻塞性肺疾病(COPD)和严重哮喘(SA)。在感染 HIV 的个体中, 肺炎的发病率降低,以及 COPD 的严重程度降低与针对 抗原 Kexin(KEX1)的天然抗体反应有关。
在一项横断面研究中,对 104 名儿科患者进行了 KEX1 IgG 倒数终点滴度(RET)检测,包括 51 名 SA 患者、20 名轻度/中度哮喘患者、20 名非哮喘患者和 13 名囊性纤维化(CF)患者。
SA 患者的 KEX1 滴度明显低于轻度/中度哮喘(p=0.018)和 CF(p=0.003)患者。确定 KEX1 RET=1000 为 KEX1 RET 的二进制指标。与轻度/中度哮喘和 CF 患者相比,SA 患者低于该阈值的几率分别为 4.40(95%CI 1.28 至 13.25,p=0.014)和 17.92(95%CI 4.15 至 66.62,p<0.001)。此外,KEX1 IgG RET 与破伤风类毒素 IgG(r=0.21,p=0.82)或总 IgE(r=0.03,p=0.76)均无相关性,表明这些发现是针对 KEX1 抗体反应的特异性发现。
由于保护性抗体水平降低,SA 儿科患者可能面临更高的慢性 感染和哮喘症状恶化风险。血浆 KEX1 IgG 滴度可能是确定哮喘儿科患者治疗临床过程的有用参数。