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| |  Gene Expression Findings May Help Classify, Predict, and Treat Juvenile Arthritis BETHESDA, Md -- July 3, 2009 -- Researchers have discovered gene expression differences that could lead to better ways to classify, predict outcome, and treat juvenile idiopathic arthritis (JIA). Eventually such findings could enable doctors to target more aggressive treatment to children at risk of more severe arthritis, while those likely to have milder disease could be spared the stronger treatments that carry a greater risk of side effects. At present, making a diagnosis of JIA is imprecise and based largely on the presence of joint inflammation persisting for at least 6 weeks, for which no other cause can be determined, said Robert A. Colbert, MD, Pediatric Translational Research Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, Maryland. Based on the number of joints involved and other clinical features, physicians classify patients into 1 of 4 or 5 major subtypes of JIA, which helps them predict a patient’s most likely outcome and guide appropriate treatments. “But, recent research suggests there is more variability in JIA than the 4 or 5 major subtypes we currently recognise,” said Dr. Colbert. In the first of 2 such studies to be published in the July issue of Arthritis & Rheumatism, researchers, led by Michael Barnes, PhD, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, used a large data set to compare a number of children newly diagnosed with 1of 4 major subtypes of JIA: (1) persistent oligoarthritis (affecting <= 4 joints); (2) polyarthritis (affecting >= 5 joints); (3) systemic arthritis (with fever and rash and inflammation throughout the body); and (4) enthesitis-related arthritis (affecting the junctions between tendons and bones). “We analysed gene expression patterns in blood cells and found that we could indeed distinguish the major subtypes of JIA,” said Dr. Colbert. “Many of the genes whose expression is altered function in the immune system. This means that not only is there immune activation, but it differs depending on the subtype of JIA that is present.” In the second study, led by Thomas Griffin, MD, also at Cincinnati Children’s Hospital Medical Center, scientists looked more closely at patients from the study with 1 particular subtype of the disease -- polyarticular JIA -- to determine if that form was more complicated, or if there were more subgroups than originally thought. They included children with rheumatoid factor (RF) positive JIA. Surprisingly, the scientists found patterns of gene expression that indicated at least 3 subgroups of polyarthritis. There was an older subgroup (mean age, 11 years) that included both RF positive and negative children with an inflammatory gene expression signature bearing some resemblance to adult RA. A second older subgroup (RF negative) had less severe arthritis and an anti-inflammatory gene expression signature. A third subgroup was comprised mostly of younger patients (mean age, 7 years) who had no clearly defined gene expression signature and did have antinuclear antibodies (ANA). This third subgroup may be more similar to oligoarthritis patients, who frequently have a positive ANA, than to the other subgroups of polyarticular JIA. “In paediatric rheumatology, we are at the early stages of improving our classification system for JIA,” said Dr. Colbert. “We expect that complementary studies designed to uncover the genetic differences that contribute to susceptibility will confirm the presence of several JIA subtypes, and add important information about what causes this group of diseases. We look forward to the day when we can use a combination of genetic and gene expression tests in the clinic to help us better diagnose and treat childhood arthritis.” SOURCE: National Institutes of Health
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