Lupus nephritis (LN) is one of the more severe systemic lupus erythematosus manifestations with the potential of developing into end stage kidney disease. Mycophenolate mofetil (MMF) and Azathioprine (AZA) are widely used for both induction and maintenance therapy for LN, but the one year complete renal response ranges from 30-40% in most trials. Reasons for non-response are still unknown. Thus, anticipating lack of drug efficacy in a patient could lead to early introduction of advanced therapies. A longitudinal cohort comprising gene-expression and clinical data of responder and non-responder samples to MMF, AZA and standar of care drugs (hidroxicloroquine (HC) and HC + glococorticoids (GC) (SOC)) was retrospectively analyzed. Response to drugs was defined over time using SRI-4 scores. Differential gene expression and functional analysis were performed. Response rate was measured based on blood cell proportions. Single-cell RNA sequencing data was analyzed to identify the cell subtypes influencing non-response and their contributing genes. SLE: Systemic Lupus Erythematosus; MMF: Mycophenolate mofetil; AZA: Azathioprine; HC: Hydroxychloroquine; PHC: Prednisone (Glucocorticoid (GC)) + HC; SOC: Standard Of Care drugs (HC and HC + PHC)
Overall design
103 and 27 responder and non-responder samples to MMF. 24 and 30 responder and non-responder samples to AZA. 133 and 40 responder and non-responder samples to HC. 173 and 64 responder and non-responder samples to SOC (HC and HC + GC). 20 healthy control samples. Preprint: https://0-doi-org.brum.beds.ac.uk/10.21203/rs.3.rs-3783877/v1
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