Center for Translational Immunology, UMC Utrecht, Utrecht, The Netherlands.
Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Eur Respir J. 2024 Oct 3;64(4). doi: 10.1183/13993003.00317-2024. Print 2024 Oct.
Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs.
We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S rRNA sequencing) and respiratory viruses (quantitative PCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink) was performed on saliva and serum samples. RTI symptoms were monitored with a daily mobile phone application and assessed using latent class analysis and negative binomial mixed models.
Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive IgA was negatively associated with recurrent lower RTIs (adjusted OR 0.80, 95% CI 0.67-0.94) and detection of multiple respiratory viruses (adjusted OR 0.76, 95% CI 0.61-0.96). abundance was positively associated with RTI symptom burden (regression coefficient 0.05, 95% CI 0.02-0.08).
These results highlight the importance of mucosal immunity in RTI severity and burden, and suggest that the level of salivary polyreactive IgA and abundance may serve as indicators of infection severity and burden in young children with rRTIs.
反复呼吸道感染（rRTIs）是儿童进行免疫诊断检测的常见原因，该检测依赖于血清抗体水平测量。然而，由于 RTIs 主要影响呼吸道黏膜，血清抗体可能无法准确反映局部免疫防御。我们研究了唾液中的抗体反应及其与呼吸道微生物群之间的相互作用，以了解 rRTIs 患儿的 RTI 严重程度和负担。
我们进行了一项前瞻性队列研究，纳入了 100 名年龄<10 岁的 rRTIs 患儿、其家庭成员和健康医护人员。通过酶联免疫吸附试验（ELISA）测定血清和唾液中的总抗体和多反应性抗体浓度；通过鼻咽拭子进行呼吸道微生物群组成（16S rRNA 测序）和呼吸道病毒（定量 PCR）的特征分析；通过 Olink 进行唾液和血清样本的蛋白质组学分析。使用每日手机应用程序监测 RTI 症状，并使用潜在类别分析和负二项式混合模型进行评估。
血清抗体水平与 RTI 严重程度无关。令人惊讶的是，28%的唾液抗体和仅 2%的血清抗体具有多反应性（p<0.001）。唾液多反应性 IgA 与复发性下呼吸道感染（调整后的 OR 0.80，95%CI 0.67-0.94）和多种呼吸道病毒的检测呈负相关（调整后的 OR 0.76，95%CI 0.61-0.96）。丰度与 RTI 症状负担呈正相关（回归系数 0.05，95%CI 0.02-0.08）。
这些结果强调了黏膜免疫在 RTI 严重程度和负担中的重要性，并表明唾液多反应性 IgA 和丰度的水平可能可作为 rRTIs 患儿感染严重程度和负担的指标。
