Identification of genes specifically over-expressed in lupus CD4 T and B cells

Objective: Gene expression studies performed on PBMC from systemic lupus erythematosus (SLE) patients provided strong evidence of a type I interferon signature, underscoring the potential role of these cytokines in the physiopathology of SLE. In this work, we performed microarray analyses of differential gene expression using purified CD4 T and B cells sorted from SLE PBMC. In order to discriminate genes specific to SLE from those induced by inflammatory responses in general, control samples were obtained not only from healthy individuals but also from rheumatoid arthritis (RA) patients. Results: A strong interferon signature was found both in the CD4 T and the B lymphocytes from SLE patients, thereby confirming the results obtained on total PBMC. Interestingly, many interferon-induced genes were also over-expressed in CD4 and B cells from RA patients. Some genes were more specifically over-expressed in SLE lymphocytes, and 3 of them, SLAMF1, BRDG1 and RASGRP1, were exclusively up-regulated in SLE B cells. SLAMF1 and BRDG1 are localized in disease-associated loci, thereby suggesting that they might play a role in the physiopathology of the disease. Keywords: Comparative analysis of global gene expression in PBMC subsets CD4 T and B cells were sorted by flow cytometry from PBMC of patients with SLE, RA and healthy controls. GeneChip® Human genome U133 Plus 2.0 arrays were hybridized in monoplicates and the genes differentially expressed among the three groups of patients were identified using ANOVA tests with corrections for multiple comparisons.