Evidence of Dynamically Dysregulated Gene Expression Pathways in Hyper-responsive B Cells from African American Lupus Patients

In this report we applied standard and original methods of analysis of gene expression microarray data to delineate differences in the molecular pathways impacted by stimulation of Epstein-Barr virus (EBV) transformed B cells derived from patients with systemic lupus erythematosus (SLE) and normal unrelated controls. In order to understand the dynamics and interconnections the B cell molecular pathways, the system was perturbed with a biologically relevant signal, co-crosslinking of the B cell antigen receptor (BCR) and FcγR2b and global gene expression changes were assessed at various timepoints post-stimulation. Both traditional analysis of differential gene expression and analysis of the dynamics of gene expression variations were performed. Combining these two methods in an analysis process we call Pathway Dysregulation Analysis allows us to establish model networks of functional gene expression important for B cell signaling responses and elucidate gene expression regulatory interconnections disrupted in B cells from individuals with lupus. Through this technique, we found two main groups of gene associations changed significantly with the disease phenotype, which included genes with established controlling function of the B cell activation, and genes involved in apoptosis initiation or prevention. Epstein-Barr virus (EBV) transformed B cells derived from two patients with systemic lupus erythematosus (SLE) and two normal unrelated controls were stimulated with a biologically relevant signal, co-crosslinking of the B cell antigen receptor (BCR) and FcγR2b. Total RNA was isolated at various timepoints post-stimulation. Gene expression data were used for analysis of differential gene expression and analysis of the dynamics of gene expression variations.