Cabanero-Navalon Marta Dafne, Carda-Diéguez Miguel, Moral Moral Pedro, Mira Alex, Balastegui-Martin Héctor, Salavert-Lletí Miguel, Garcia-Bustos Victor
Primary Immunodeficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe, 46026 Valencia, Spain.
Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe, 46026 Valencia, Spain.
Biomedicines. 2024 Oct 1;12(10):2239. doi: 10.3390/biomedicines12102239.
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections, with non-infectious complications such as granulomatous-lymphocytic interstitial lung disease (GLILD) affecting up to 30% of patients. Using high-throughput 16S rRNA gene sequencing, salivary, sputum, and fecal microbiome from CVID patients with GLILD, comparing them to CVID patients without GLILD-with immune dysregulation (dCVID) and only infections (iCVID)-and healthy controls was analyzed. A total of 41 CVID patients, 7 with GLILD, and 15 healthy donors were included. Global fecal biodiversity was significantly lower in GLILD patients compared to CVID subgroups and controls. GLILD patients harbored different specific bacterial communities in all niches, with some keystone species common to dCVID. , , and are more frequent in the sputum of GLILD patients. Saliva in GLILD shows higher frequencies of and . Fecal samples from GLILD patients have higher levels of , , and . A non-assigned spp. is consistently associated with GLILD across different niches and could be a potential pathobiont or relevant microbiological marker for GLILD. Cluster network and correlation analyses show profound dysbiosis in the sputum, saliva, and feces of GLILD patients. These findings highlight significant microbiome alterations in CVID patients with GLILD, particularly in the respiratory tract, suggesting a possible link to both local and systemic immune dysregulation.
普通可变免疫缺陷（CVID）是一种原发性免疫缺陷，其特征为免疫球蛋白减少和反复感染，高达30%的患者会出现肉芽肿性淋巴细胞间质性肺病（GLILD）等非感染性并发症。利用高通量16S rRNA基因测序技术，对患有GLILD的CVID患者的唾液、痰液和粪便微生物群进行了分析，并将其与无GLILD的CVID患者（伴有免疫失调，即dCVID和仅有感染，即iCVID）以及健康对照进行比较。总共纳入了41名CVID患者，其中7名患有GLILD，还有15名健康供体。与CVID亚组和对照组相比，GLILD患者的总体粪便生物多样性显著降低。GLILD患者在所有生态位中都拥有不同的特定细菌群落，其中一些关键物种与dCVID相同。 、 和 在GLILD患者的痰液中更为常见。GLILD患者唾液中 和 的出现频率更高。GLILD患者的粪便样本中 、 和 的水平更高。一种未分类的 属细菌在不同生态位中均与GLILD持续相关，可能是GLILD的潜在致病共生菌或相关微生物标志物。聚类网络和相关性分析显示，GLILD患者的痰液、唾液和粪便中存在严重的生态失调。这些发现突出了患有GLILD的CVID患者，尤其是呼吸道中的微生物群显著改变，提示其可能与局部和全身免疫失调存在关联。
