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NEJM editorial on significance and limitations of new lupus gene expression research
Date:1/20/2008

lthy individuals without the disease. This small variation may alter the expression or function of the protein encoded by that gene in a way that contributes to the disease.

Two of the studies are comprehensive reports of genomewide analyses looking for these types of small changes, specifically for those that appear more frequently in lupus patients and could predispose them to the disease. A third study also used a total genome analysis but focuses on those SNPs that are predicted to change the amino acid sequence of the protein product, meaning there is a greater chance the resulting proteins expression, role or activity is changed. The fourth study centers around one gene in particular, called ITGAM.

These genetic studies are the first step in getting a detailed understanding of the molecular pathways that underlie lupus, says Dr. Crow. The results help direct researchers to the genes, molecules and cells that are directly involved in the disease so that they can eventually identify exactly which pathways they can target therapeutically.

Dr. Crow was particularly intrigued by the research on ITGAM, whose association with lupus was supported by three of the new studies. The protein encoded by ITGAM is found on the immune systems white blood cells that are recruited to blood vessels when it is activated. Some of the characteristic clinical features of lupus involve changes in blood vessels, including alterations in the kidneys, eyes, skin and the premature atherosclerosis that is common in lupus patients. The ITGAM protein, which is an adhesion molecule, helps leukocytes adhere to the cells lining blood vessels. The new genetic analysis of ITGAM variations associated with the disease predicts that it may promote vascular inflammation.

The role of the target tissue, such as the blood vessels, had been prominent in early lupus research, says Dr. Crow, but in the past 25 to 30 years the focus has been primarily on the immune s
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Contact: Phyllis Fisher
fisherp@hss.edu
212-606-1197
Hospital for Special Surgery
Source:Eurekalert

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