Interindividual Variability in Lymphocyte Stimulation and Transcriptomic Response Predicts Mycophenolic Acid Sensitivity in Healthy Volunteers.

ABSTRACT: Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single-cell RNA-sequencing (n ± 6) in lymphocyt

SUBMITTER: Collins KS 

PROVIDER: S-EPMC7719379 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature