Abstract
Common Variable Immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are primary antibody deficiencies characterized by hypogammaglobulinemia and recurrent infections, which can lead to structural airway disease (AD) and interstitial lung disease (ILD). We investigated associations between serum IgA, oropharyngeal microbiota composition and severity of lung disease in these patients. In this cross-sectional multicentre study we analyzed oropharyngeal microbiota composition of 86 CVID patients, 12 XLA patients and 49 healthy controls (HC) using next-generation sequencing of the 16S rRNA gene. qPCR was used to estimate bacterial load. IgA was measured in serum. High resolution CT scans were scored for severity of AD and ILD. Oropharyngeal bacterial load was increased in CVID patients with low IgA (p = 0.013) and XLA (p = 0.029) compared to HC. IgA status was associated with distinct beta (between-sample) diversity (p = 0.039), enrichment of (Allo)prevotella, and more severe radiographic lung disease (p = 0.003), independently of recent antibiotic use. AD scores were positively associated with Prevotella, Alloprevotella, and Selenomonas, and ILD scores with Streptococcus and negatively with Rothia. In clinically stable patients with CVID and XLA, radiographic lung disease was associated with IgA deficiency and expansion of distinct oropharyngeal bacterial taxa. Our findings highlight IgA as a potential driver of upper respiratory tract microbiota homeostasis.
Highlights
The microbiota of the respiratory tract is increasingly recognized as an important driver of respiratory health [1], and has been associated with susceptibility to infection [2], hypersensitivity reactions such as asthma [3], and immunemediated lung disease such as sarcoidosis [4]
Oropharyngeal swabs were collected from 86 common variable immunodeficiency (CVID) patients, 49 healthy controls (HC) and 12 X-linked agammaglobulinemia (XLA) patients (Table 1) in two academic hospitals in Rotterdam and Utrecht, the Netherlands
We observed that bacterial load, alpha diversity and relative abundance of bacteria from the Prevotellaceae family were consistently increased in patients with more profound IgA deficiency, CVID-IgA and XLA
Summary
The microbiota of the respiratory tract is increasingly recognized as an important driver of respiratory health [1], and has been associated with susceptibility to infection [2], hypersensitivity reactions such as asthma [3], and immunemediated lung disease such as sarcoidosis [4]. Studying the microbiota of patients with primary antibody deficiency such as common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) can provide insight into the role and importance of the humoral immune system in controlling the microbiota [8]. The antibody deficiency in CVID is defined as low IgG, and either low IgA or IgM, or both [9]. While CVID can develop later in life and its causes are thought to be multifactorial [9], XLA is a congenital disease that is the result of a mutation in Bruton’s tyrosine kinase, resulting in an early B cell defect and complete humoral immunodeficiency from birth, including IgG, IgA and IgM [12]
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