A candidate biomarker to improve treatment of lupus patients

(2005-05-06)

Study associates high expression of interferon induced genes with increased disease severity, including kidney disease

A chronic disease of the immune system, systemic lupus erythematosus (SLE) affects approximately 1.5 million people nationwide, according to the Lupus Foundation of America. Characterized by the production of autoantibodies throughout the body, SLE affects women more than men and can cause problems ranging from skin rash and joint pain to kidney failure and stroke. The wide range of disease symptoms among patients can make SLE difficult to diagnose and treat, especially since current laboratory tests or biomarkers have limitations.

A recent study provides the basis for a new laboratory biomarker to better evaluate new therapies as well as to help doctors more effectively treat lupus patients at risk for serious complications. Published in the May 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), the findings shed important light on the role of interferon, a protein critical to immunity released into the bloodstream, in the progression of SLE.

Supported by the Alliance for Lupus Research, the Lupus Research Institute, the Mary Kirkland Center for Lupus Research, and the NIH, the study was conducted by a team of researchers with the Kirkland Center, Hospital for Special Surgery, and Weill Medical College of Cornell University in New York City. Led by Kyriakos A. Kirou, M.D. and Mary K. Crow, M.D., the team set out to test the hypothesis that activation of a particular interferon pathway-- the type I interferon pathway--is more common among SLE patients with the highest disease activity. Activation of this pathway is indicated by high levels of expression of interferon-inducible genes (IFIGs) in peripheral blood mononuclear cells.

The team collected blood samples from 77 SLE patients, 22 disease controls (20 with rheumatoid arthritis and 2 with autoimmune uveitis), and 28 healthy controls. Drs. Kirou and Crow and their associates made an effort to match SLE patients with both control groups with regard to sex--with women as the majority--and race, with progressively decreasing ratios of whites, African-Americans, Asians, and Hispanics. In addition, the SLE patients and disease controls were well matched for age, disease duration, and daily prednisone dose. The team also gathered relevant clinical data on the SLE patients. Then, they analyzed and compared all the blood samples for levels of IFIG expression. Overall, SLE patients scored higher than the other disease patients, as well as the healthy donors, for activation of the type I interferon pathway. Among SLE patients, the highest scoring group was strongly associated with increased disease severity, increased disease activity, and certain autoantibodies known to react with proteins that bind to the important nucleic acid, RNA. SLE patients with high scores were also more likely to suffer from kidney disease.

"Our data have defined a subgroup of SLE patients who have more severe disease, with frequent kidney involvement, and more active disease, as measured by complement activation, suggesting that determination of IFIG expression may prove a useful approach to selection of patients for clinical studies," states Dr. Kirou. "Our next challenge will be to plan clinical studies to validate the measurement of IFIG as a biomarker for active lupus." Beyond its clinical applications, this study provides new clues to the underlying mechanisms that drive autoimmunity.

Article: "Activation of the Interferon-á Pathway Identifies a Subgroup of Systemic Lupus Erythematosus Patients With Distinct Serologic Features and Active Disease," Kyriakos A. Kirou, Christina Lee, Sandhya George, Kyriakos Louca, Margaret G.E. Peterson, and Mary K. Crow, Arthritis & Rheumatism, May 2005; 52:5; pp. 1491-1503.

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