常见可变免疫缺陷
免疫系统
布鲁顿酪氨酸激酶
免疫学
免疫缺陷
抗体
先天免疫系统
生物
原发性免疫缺陷
酪氨酸激酶
信号转导
遗传学
作者
Hsi-en Ho,Lin Radigan,Gerold Bongers,Ahmed El-Shamy,Charlotte Cunningham-Rundles
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2021-10-08
卷期号:6 (19)
被引量:8
标识
DOI:10.1172/jci.insight.144777
摘要
Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging to gut commensals was significantly increased in CVID serum (P < 0.0001), especially in patients with inflammatory manifestations (P = 0.0007). Levels of serum bacterial DNA were associated with parameters of systemic immune activation, increased serum IFN-γ, and the lowest numbers of isotype-switched memory B cells. Bacterial DNA was bioactive in vitro and induced robust host IFN-γ responses, especially among patients with CVID with inflammatory manifestations. Patients with X-linked agammaglobulinemia (Bruton tyrosine kinase [BTK] deficiency) also had increased circulating bacterial 16S rDNA but did not exhibit prominent immune activation, suggesting that BTK may be a host modifier, dampening immune responses to microbial translocation. These data reveal a mechanism for chronic immune activation in CVID and potential therapeutic strategies to modify the clinical outcomes of this disease.
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