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Pediatric researchers find possible 'master switch' gene in juvenile arthritis
July 02, 2008Researchers have found that a gene region known to play a role in some varieties of adult rheumatoid arthritis is also present in all types of childhood arthritis. The researchers say the responsible gene may be a "master switch" that helps turn on the debilitating disease.
Researchers at The Children's Hospital of Philadelphia reported on the link between the gene region and juvenile idiopathic arthritis (JIA), formerly called juvenile rheumatoid arthritis. The genetic variant is on chromosome 9 in a region housing two genes, TRAF1 and C5. The TRAF1 gene codes for a protein that regulates tumor necrosis factor, a chemical strongly associated with JIA. However, the researchers say further study is needed to determine whether the TRAF1 gene or the C5 gene is altered in the disease.
The study appears in the July 2008 issue of Arthritis & Rheumatism. Lead authors are Terri H. Finkel, M.D., Ph.D.; Hakon Hakonarson, M.D. Ph.D., director of the Center for Applied Genomics; and Edward M. Behrens, M.D., all of Children's Hospital.
"There are only a few genes that may act as master switches like this to regulate autoimmune diseases," said Finkel, the chief of Rheumatology at Children's Hospital. "This switch we discovered probably has to be an 'ON' gene and when it interacts with other genes and environmental triggers, a child may get juvenile arthritis."
The study compared 67 Caucasian patients being treated for JIA to 1,952 healthy Caucasian control subjects recruited within the hospital's patient network. While the cause of JIA is unknown, results from this study back up past research that shows arthritis arises in a genetically susceptible individual due to environmental factors.
About 300,000 children in the U.S. have JIA, of which about 1,500 children are seen at Children's Hospital. JIA is the inflammation of the lining tissues of a joint and often causes stiffness and pain. While there is no cure for JIA, medicines and physical therapy can help maintain movement and reduce swelling and pain. Researchers have previously identified seven subtypes of JIA.
"We think this finding may be a clue to the specific disease pathway that leads to arthritis," said Behrens, a pediatric rheumatologist at Children's Hospital. "We currently use medicines called tumor necrosis factor blockers to treat children with JIA. However, not all children respond to these drugs, and other children may develop severe allergic reactions and other side effects. If we can fully identify all the genes that interact with environmental risk factors, we might develop more targeted treatments with fewer side effects."
"The high-resolution genome-wide association approach has very markedly enhanced our ability to identify disease genes in complex disorders such as JIA, and what is remarkable about this discovery is that it appears there may be a common genetic factor predisposing to all seven forms of the disease," said Dr. Hakonarson.
Children's Hospital of Philadelphia
"There are only a few genes that may act as master switches like this to regulate autoimmune diseases," said Finkel, the chief of Rheumatology at Children's Hospital. "This switch we discovered probably has to be an 'ON' gene and when it interacts with other genes and environmental triggers, a child may get juvenile arthritis."
The study compared 67 Caucasian patients being treated for JIA to 1,952 healthy Caucasian control subjects recruited within the hospital's patient network. While the cause of JIA is unknown, results from this study back up past research that shows arthritis arises in a genetically susceptible individual due to environmental factors.
About 300,000 children in the U.S. have JIA, of which about 1,500 children are seen at Children's Hospital. JIA is the inflammation of the lining tissues of a joint and often causes stiffness and pain. While there is no cure for JIA, medicines and physical therapy can help maintain movement and reduce swelling and pain. Researchers have previously identified seven subtypes of JIA.
"We think this finding may be a clue to the specific disease pathway that leads to arthritis," said Behrens, a pediatric rheumatologist at Children's Hospital. "We currently use medicines called tumor necrosis factor blockers to treat children with JIA. However, not all children respond to these drugs, and other children may develop severe allergic reactions and other side effects. If we can fully identify all the genes that interact with environmental risk factors, we might develop more targeted treatments with fewer side effects."
"The high-resolution genome-wide association approach has very markedly enhanced our ability to identify disease genes in complex disorders such as JIA, and what is remarkable about this discovery is that it appears there may be a common genetic factor predisposing to all seven forms of the disease," said Dr. Hakonarson.
Children's Hospital of Philadelphia
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Rheumatoid Arthritis Current Events and Rheumatoid Arthritis News RSSGene expression findings a step toward better classification and treatment of juvenile arthritis
Scientists have discovered gene expression differences that could lead to better ways to classify, predict outcome, and treat juvenile idiopathic arthritis (JIA).
New trigger for chronic inflammation in rheumatoid arthritis discovered
A signal molecule made by the human body that triggers the immune system into action may be important in rheumatoid arthritis.
Structures from the human immune system's oldest branch shed light on a range of diseases
How molecules of the oldest branch of the human immune system have interconnected has remained a mystery.
Psoriasis associated with cardiovascular disease and increased mortality
The skin disease psoriasis is associated with atherosclerosis (a buildup of plaque in the arteries) characterized by an increased prevalence of ischemic heart disease, cerebrovascular disease, peripheral artery disease and an increased risk of death.
Early treatment of systemic onset JIA with anakinra restores the IL-18 response
First line treatment with anakinra (an interleukin-1 (IL-1) receptor antagonist), results in a 'good' clinical response (ACRp90) in patients newly diagnosed with systemic onset juvenile idiopathic arthritis (SoJIA), and restores the deficient IL-18 response of natural killer (NK) cells.
RA individuals from lower GDP countries keep working despite worse symptoms than richer countries
Individuals diagnosed with rheumatoid arthritis (RA) in lower gross domestic product (GDP) countries (GDP below $11,000) are more likely to continue working despite higher disease activity and functional disability scores compared to their counterparts in higher GDP countries (GDP >$24,000).
Aussie and Kiwi researchers make double MS genetic discovery
Australian and New Zealand researchers have accelerated research into Multiple Sclerosis by discovering two new locations of genes which will help to unravel the causes of MS and other autoimmune disease.
New treatment strategy offers hope to RA patients who failed all other therapies
Rheumatoid arthritis (RA) patients who failed to respond to initial treatment with rituximab (RTX) (a chimeric monoclonal antibody against the protein CD20) can still be successfully re-treated with a second course of RTX after six months.
Diagnosis of arthritis 5 years earlier in childless women compared to those with children
Nulliparous women (those who have not given birth to children) are diagnosed with chronic arthritides (including ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis (RA) an average of 5.2 years before parous women (those who have given birth to children).
63 percent of RA patients suffer psychiatric disorders, with depressive spectrum conditions most likely
Over half (63%) of patients with rheumatoid arthritis (RA) also suffer from psychiatric disorders, with the majority of these (87%) occurring in the depressive spectrum.
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