Microarray analysis of gene expression in lupus

Abstract

Recent advances in the study of global patterns of gene expression with the use of microarray technology, coupled with data analysis using sophisticated statistical algorithms, have provided new insights into pathogenic mechanisms of disease. Complementary and reproducible data from multiple laboratories have documented the feasibility of analysis of heterogeneous populations of peripheral blood mononuclear cells from patients with rheumatic diseases through use of this powerful technology. Although some patterns of gene expression, including increased expression of immune system cell surface activation molecules, confirm previous data obtained with other techniques, some novel genes that are differentially expressed have been identified. Most interesting is the dominant pattern of interferon-induced gene expression detected among blood mononuclear cells from patients with systemic lupus erythematosus and juvenile dermatomyositis. These data are consistent with longstanding observations indicating increased circulating interferon-alpha in the blood of patients with active lupus, but draw attention to the dominance of the interferon pathway in the hierarchy of gene expression pathways implicated in systemic autoimmunity.

Figure 1

Exemplary gene sequences that cluster with PRKR and OAS3. Hierarchical clustering was performed on the total study population to determine genes that cluster with PRKR and OAS3. A visual demonstration of the expression of a selection from those genes, comprising a partial IFN signature, is shown. Data are shown from a subset of SLE samples tested (n = 14) and from rheumatoid arthritis (RA) (n = 11), juvenile chronic arthritis (JCA) (n = 2), and control samples (n = 8). Relative expression compared with an internal control ranged from approximately -0.5 (bright green) to 0.5 (bright red).