mRNA and miRNA Screening to Identify Treatment Responses in SLE Patients Receiving Belimumab. mRNA and miRNA Screening to Identify Treatment Responses in SLE Patients Receiving Belimumab

Systemic lupus erythematosus (SLE) is a complex autoimmune disease driven by autoreactive B cells and the cytokine BAFF (BLyS), which is vital for B-cell function. Despite advances in genomics, no clear profile exists to predict which patients benefit most from BLyS-targeted therapies. miRNAs, small noncoding RNAs, regulate numerous cellular activities and have emerged as potential biomarkers for autoimmune diseases like SLE. Dysregulated miRNAs in SLE T and B cells contribute to immune hyperactivation, promoting autoantibody production and heightened type 1 interferon levels. While miRNAs are promising diagnostic tools, their role in predicting responses to anti-BLyS therapy remains unexplored. This study examines miRNA-mRNA interaction networks in T cells, B cells, and myeloid cells from SLE patients before and after BLyS therapy, identifying differentially expressed miRNAs and mRNAs. Integrative analyses reveal novel regulatory networks and pathways associated with clinical improvement, offering new insights into the pharmacological mechanisms of anti-BLyS therapy. Overall design: PBMCs were sorted using spectral cytometry to isolate B cells, T cells, and myeloid cell populations. RNA and miRNA were extracted from each subset, followed by a microarray analysis. Gene expression profiling was conducted using the Clariom S assay, and miRNA expression profiling was performed with GeneChip miRNA 4.0 arrays (Thermo Fisher Scientific, Inc.).