Inter-individual variability in lymphocyte stimulation and transcriptomic response predicts mycophenolic acid sensitivity in healthy volunteers

Mycophenolic acid is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. Despite its widespread use, there is a clinical need to reduce solid-organ transplant rejection and improve rates of complete therapeutic response in autoimmunity. Single-cell RNA-sequencing (n=6) in lymphocytes was performed at baseline, post-stimulation, and post-mycophenolate treatment. This study identifies a polygenic transcriptomic signature in lymphocyte sub-populations predictive of mycophenolate response. Overall design: Lymphocytes were sequenced at baseline (after Ficoll Isolation), post-stimulation (antibodies to CD3/CD28), and post-MPA treatment (1 µg/mL).