IL-4 receptor blockade is a global repressor of naive B cell development and responses in a dupilumab-treated patient

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.

Automated summary

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.