Data_Sheet_1_Low IgA Associated With Oropharyngeal Microbiota Changes and Lung Disease in Primary Antibody Deficiency.docx

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.

常见可变免疫缺陷病（CVID）和X连锁无丙种球蛋白血症（XLA）均为原发性抗体缺陷，以低丙种球蛋白血症和反复感染为特征，可能导致结构性气道疾病（AD）和间质性肺疾病（ILD）。本研究旨在探讨血清IgA、口腔咽部微生物群落组成与这些患者肺疾病严重程度之间的关联。在本项横断面多中心研究中，我们利用16S rRNA基因的下一代测序技术分析了86名CVID患者、12名XLA患者和49名健康对照者（HC）的口腔咽部微生物群落组成。采用qPCR技术估算细菌负荷。血清中测量IgA水平。通过高分辨率CT扫描评估AD和ILD的严重程度。与HC相比，CVID患者中低IgA（p = 0.013）和XLA（p = 0.029）患者的口腔咽部细菌负荷增加。IgA状态与不同的β（样本间）多样性（p = 0.039）相关，以及（Allo）普雷沃菌的富集，以及更严重的影像学肺疾病（p = 0.003），且这种关联独立于近期抗生素的使用。AD评分与普雷沃菌、Allo普雷沃菌和席莱门菌呈正相关，而ILD评分与链球菌呈正相关，与罗氏菌呈负相关。在临床稳定的CVID和XLA患者中，影像学肺疾病与IgA缺乏和特定口腔咽部细菌类群的扩张相关。我们的研究结果表明，IgA可能是上呼吸道微生物群落稳态的潜在驱动因素。