IL-4 receptor blockade is a global repressor of naïve 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 α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve 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+ naïve 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 anti-receptor 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 naïve B cells, and maintaining a long term vaccine response. We carried out single cell RNAseq for four individuals. Subjects recruited for this study: bi-weekly dupilumab-treated subject is a 34-year-old white male with AD and celiac disease. Control #1 (Con#1) is a 57-yr-old white healthy male and Con#2 is a 53-yr-old white healthy male. Con#3 is a 57-year-old, Asian female with AD controlled by intermittent treatment with topical 0.05% Fluocinonide.