Microarray Exploration of the Infection Autoimmune Disease Linkage

Infection Autoimmune Disease

The relatively new technology of DNA microarrays has made it feasible to measure the expression levels of thousands of genes in small biological samples. It has been suggested that this methodology might be especially useful in analyzing the complex and parallel changes that occur within cells and tissues of the immune system in normal and pathologic states. Much of the early work using DNA microarrays was in the field of oncology; other studies have examined host responses to infectious agents or drugs.

The gene array approach is especially well-suited to the type of multifactorial analysis that is needed to unravel the causes of human autoimmune disorders that involve both complex genetics and environmental factors. Studies in autoimmune disease have included the use of biopsy samples from affected patients, targeting tissues such as synovium, brain or skin. While this approach can offer insights for some disease subsets, it does not permit study of all afflicted patients and cannot be applied to early phases of disease when therapeutic interventions are most likely to be useful.

As an alternative, we and others have hypothesized that due to the systemic nature of autoimmune disease, clinically relevant changes in gene expression should be observed in peripheral blood mononuclear cells (PBMCs). Using peripheral blood as the source of gene expression material offers the possibility of sampling any individual at any time and also has the potential to detect early pathogenetic and prognostic factors. This review will examine studies in autoimmune disease, focusing on the utility of peripheral blood samples to identify genes of interest. The potential for this approach to provide insights into disease pathogenesis and to aid with diagnosis and management are also discussed.

Microarray Exploration of the Infection Autoimmune Disease Linkage

A relatively small number of microarray studies in autoimmunity have been reported. Some of these have used animal models, such as for alopecia areata and experimental systemic lupus erythematosus (SLE). In human autoimmunity, biopsy samples from tissues such as rheumatoid synovium and skin have yielded disease insights. Other groups of investigators have concentrated on the possibility that peripheral blood might show gene expression correlations with disease states.

Six published reports have described results obtained using microarray analysis of PBMC populations from patients with various autoimmune disorders . Two of these studies were in multiple sclerosis (MS) and three were in SLE, including one that used only juvenile subjects. In a study from our own laboratory, four different autoimmune diseases, rheumatoid arthritis (RA), SLE, MS and Type-I or insulin-dependent diabetes mellitus (IDDM), were studied.

The diseases represented in these reports span a broad spectrum within the rubric of autoimmunity, including both generalized (RA and SLE) and tissue-specific (MS and IDDM) pathologies. Three of these syndromes (RA, SLE and MS) show a female predominance, while IDDM in humans has no significant gender dimorphism. Treatments also differ, with RA and SLE usually requiring long-term continuous immune suppression, while MS often shows quiescent phases requiring no treatment and IDDM therapies are for glucose control rather than immune suppression.

In most published studies, autoimmune samples have been compared to unaffected control individuals who are generally matched for the age and gender characteristics of the study population. Our group also investigated the relationship between a normal immune response and the autoimmune response by examining control subjects before and after routine influenza vaccination.

It is notable that in most of these reports, the numbers of samples are relatively small, with significant results reported using study groups of 10–20 subjects each, indicating the strength of the multiparameter approach to analysis of array data. Many investigators have used frozen samples, which permit added flexibility for approaches such as studies of longitudinal responses to a therapeutic intervention.

Random Posts