期刊
CLINICAL IMMUNOLOGY
卷 244, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2022.109130
关键词
IL-4 receptor; Dupilumab; Naive B cells; Memory B cells; COVID-19 vaccination
类别
资金
- VA Merit Review grant [1I01BX005448, I01BX004049]
- National Institutes of Health [R01 AI134023]
- VA CSRD Supplemental Funding Award [COVID198900-04]
- Lupus Research Alliance-Target Identification in Lupus Award
- NIH [AR-048311, P30-AI-027767]
In this study, a patient with atopic dermatitis treated with dupilumab showed a decrease in IL4R expression in naive B cells, leading to apoptosis and inhibition of B cell signaling. Additionally, the patient exhibited a rapid decline in COVID-19 antibody levels post-vaccination.
Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor a chain (IL-4R alpha). Single cell RNA-sequencing showed that naive B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naive B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and antireceptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naive B cells, and maintaining a long term vaccine response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据