Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus glomerulonephritis

Abstract

Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donors to explore potential pathways for clinical intervention. Leukocyte gene expression profiles were determined on Affymetrix U133A/B chips in 88 autoimmune patients, 28 healthy donors, and healthy donor leukocyte cell subtypes that were activated in vitro. Comparison of gene expression in leukocytes identified differentially expressed signature genes that distinguish each donor source. The microarray expression levels for many signature genes correlated with the clinical activity of small vessel vasculitis in the ANCA patients; a result confirmed by quantitative real time-polymerase chain reaction for 16 relevant genes. Comparison with in vitro-activated leukocyte subtypes from healthy donors revealed that the ANCA signature genes were expressed by neutrophils while the SLE signature genes were expressed in activated monocytes and T cells. We have found that leukocyte gene expression data can differentiate patients with RA, SLE, and ANCA-related small vessel vasculitis. Monitoring changes in the expression of specific genes may be a tool to help quantify disease activity during treatment.