Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus

Abstract

SUMMARYAutoimmune diseases are either tissue-specific like multiple sclerosis (MS) or multisystemic like systemic lupus erythematosus (SLE), although clinically both exhibit common features. To gain insight into the properties of the genes involved in each disease we have investigated the gene expression signature of peripheral blood mononuclear cells (PBMC) in MS and SLE in comparison to healthy subjects. Total RNA was purified, hybridized to Genechip array and analysed in 36 subjects (13 relapsing-remitting MS patients, five SLE patients and 18 age-matched healthy subjects that served as controls). Additional blood samples from 15 relapsing-remitting MS patients, 8 SLE patients and 10 healthy subjects were used for confirmation of microarray gene expression findings by ELISA and RT-PCR. MS and SLE patients demonstrated a common gene expression autoimmune signature of 541 genes which differentiated them from healthy subjects. The autoimmune signature included genes that encode proteins involved in apoptosis, cell cycle, inflammation and regulation of matrix metalloproteinase pathways. Specifically, decreased TIMP1 gene expression in the autoimmunity signature suggests increased MMP activity in target tissues as a result of the lack of feedback mechanism. An additional different disease specific signature identified the gene expression pattern for MS (1031 genes), mainly associated with over-expression of adhesion molecules and down-expression of heat shock proteins; the SLE specific signature (1146 genes) mainly involved DNA damage/repair pathways that result in production of nuclear autoantibodies.These results provide insights into the genetic pathways underlying autoimmune diseases, and identify specific disease-associated signatures that may enable targetted disease-related specific therapies to be developed.

Heat Shock Protein 70: Roles in Multiple Sclerosis

“…Nevertheless, controversial differences between MS patients and healthy controls have been found in gene expression studies. Whereas earlier genetic studies showed HSPA1A overexpression in MS lesions (64,65,68), more recently HSPA1A expression was shown to be downregulated in the PBMC of MS patients (141)(142)(143). Histological studies in MS and EAE tissues have confirmed HSPA1A upregulation in CNS lesions; however, surprisingly, analysis of the baseline expression of Hsp70 genes in PBMC revealed no differences among MS patients, healthy controls or patients with rheumatoid arthritis.…”

Altered gene expression in mice with lupus treated with edratide, a peptide that ameliorates the disease manifestations

“…Recently, microarray analysis in the case of sev-eral autoimmune diseases (SLE, rheumatoid arthritis, multiple sclerosis, and type I diabetes) was found to yield a common expression signature (17,40). The genes that we identified might be unique to SLE, or they might be genes with potential relevance for other autoimmune diseases as well.…”

“…Rus et al (15) showed, for example, that transcripts of Tnfsf10 (encoding TRAIL) as well as transcripts of Tnfsf10C and Tnfsf10D (both encoding TRAIL receptors) were increased in PBMCs from lupus patients relative to controls. Also, Tnfsf9 was one of the genes shown to differentiate PBMCs of SLE patients from those of healthy controls (40).…”

Gene expression profiling and association studies implicate the neuregulin signaling pathway in Behçet's disease susceptibility

“…Gene profiling experiments have allowed the identification of novel and unsuspected pathways involved in disease etiology, including in rheumatic and immune diseases [4][5][6]. Pathway analysis of differentially expressed genes is a useful approach to highlight undetected patterns in the data and to determine which differentially expressed genes to follow-up in independent assays such as association studies.…”