Although in its infancy, the use of microarrays in autoimmune diseases has already proved the value of this technology. Gene expression profiling has provided insight into the heterogeneity of autoimmune diseases. For most autoimmune diseases, the specific cell types involved in the disease are usually not known, which proposes a special challenge for autoimmune research.

The ability of GeneChip® technology to allow the elucidation of expression signatures that contain thousands of genes in an unbiased assay is particularly well suited for researchers studying this type of disease. Great scientific advances in diseases such as lupus, type I diabetes, multiple myeloma and rheumathoid arthritis, to name a few, have already been accomplished using this technological approach.

Lupus

Several groups have used GeneChip® arrays to study the differential gene expression of blood cells in patients with lupus, and have implicated a group of genes in the pathogenesis of the disease. Han et al. for example, studied 10 Chinese patients with Lupus and even though the sample size was small, was able to identify 61 genes that exhibited different activity when compared to normal controls, and showed that some interferon-inducible genes were frequently upregulated in these patients. Consistent with these results, Baechler et al. (2003) studied more than 40 lupus patients, and were able to show a correlation between the interferon-induced gene group and the patients’ clinical manifestations.

Rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease in which the immune system attacks normal tissue. The inflammation associated with rheumatoid arthritis primarily attacks the linings of the joints. Patients that have this disease respond very differently to a variety of therapeutic drugs, including anti-TNF (tumor necrosis factor) therapy. TNF-alpha is a protein that is known to provoke inflammation, and biologic agents that target this protein have been successfully used to curtail the activity of rheumatoid arthritis. The genes regulated by TNF-alpha have been studied in detail (Zhang, et al. 2004). Current research is focusing on gene expression profiling to stratify patients on the basis of their response to anti-TNF therapy.

It is evident that gene expression profiling is enabling advances in immunology research. In addition, the availability of novel approaches for large-scale, high-throughput genotyping allows whole-genome linkage studies to be accomplished. This type of study was performed in a cohort of late-onset rheumatoid arthritis patients (John, et al. 2004). This group of researchers was able to describe the first application of this technology to this disease, and directly compare the results with those stemming form microsatellite experiments.

Multiple Myeloma

Allogeneic bone marrow or autologous peripheral blood stem cell transplantation, in addition to chemotherapy, is currently considered standard therapy for young patients with multiple myeloma. Gene expression profiling has been used to clarify the mechanisms by which a patient becomes responsive or resistant to new and established drugs, such as thalidomide and PS341 proteosome inhibitor (Shaugnessy, et al. 2002). This approach has already revealed unique drug-induced alterations in gene expression that shed light upon the molecular mechanisms underlying the response or resistance of myeloma to established and new agents. In the future, this may allow for more personalized therapies by allowing the stratification of patients in terms of their responsiveness to novel and established drugs.

Type I diabetes

Type I diabetes is an autoimmune disease in which the immune system (T-cells) attacks the insulin-producing B-cells in the pancreas, resulting in insulitis and ultimately, hyperglycemia. Microarray experiments have been used to elucidate the molecular mechanisms that regulate the transformation of insulitis into diabetes, the hyperglycemic pathogenic state, which is of great therapeutic importance. In addition, these experiments resulted in the identification of the natural killer cell (NK) profile, and suggested a role for this cell type in type I diabetes (Poirot, et al. 2004).

These are just a few examples of diseases where GeneChip® technology has enabled scientific advances.

As in many cancer examples, microarray studies in immunology will lead to the discovery of clinically relevant biomarkers that will allow the detailed diagnosis and a more personalized therapy selection to manage these difficult disorders.