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A candidate biomarker to improve treatment of lupus patients
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.
John Wiley & Sons, Inc.
http://www.interscience.wiley.com
Un candidat pentru a îmbunãtãþi biomarker de tratament a pacienþilor lupus - A candidate biomarker to improve treatment of lupus patients - articole medicale engleza - startsanatate