MEDICAL: GENETICS : MEDICAL: CONDITIONS: ARTHRITIS: Gene Expression Findings a Step Toward Better Classification and Treatment of Juvenile Arthritis

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MEDICAL: GENETICS : MEDICAL: CONDITIONS: ARTHRITIS: Gene Expression Findings a Step Toward Better Classification and Treatment of Juvenile Arthritis

David P. Dillard
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MEDICAL: GENETICS :
MEDICAL: CONDITIONS: ARTHRITIS:
Gene Expression Findings a Step Toward
Better Classification and Treatment of Juvenile Arthritis



Date: Mon, 29 Jun 2009 12:05:48 -0400
From: "NIH OLIB (NIH/OD)" <[hidden email]>
To: [hidden email]
Subject:  Gene Expression Findings a Step Toward
Better Classification and Treatment of Juvenile Arthritis




U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News


National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS)
<http://www.niams.nih.gov/>



Embargoed for Release: Monday, June 29, 2009, 12:00 p.m. EDT



CONTACT:

Trish Reynolds

301-496-8190

e-mail:

[hidden email]



GENE 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). 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. The researchers were
supported by the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), a part of the National Institutes of Health.

JIA is an inflammatory and sometimes disabling joint disease that affects
an estimated 294,000 children in the United States. At present, making a
diagnosis of JIA is imprecise and based largely on the presence of joint
inflammation persisting for at least six weeks, for which no other cause
can be determined, says Robert A. Colbert, M.D., Ph.D., chief of the NIAMS
Pediatric Translational Research Branch. Based on the number of joints
involved and other clinical features (fever and rash, for example),
doctors classify patients into one of four or five 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 four or five major subtypes we currently
recognize," Dr. Colbert says.

In the first of two such NIAMS-supported studies to be published in the
July issue of Arthritis & Rheumatism, scientists led by Michael Barnes,
Ph.D., of Cincinnati Children's Hospital Medical Center used a large data
set to compare a number of children newly diagnosed with one of four major
subtypes of JIA -- persistent oligoarthritis (affecting four or fewer
joints), polyarthritis (affecting five or more joints), systemic arthritis
(with fever and rash and inflammation throughout the body) and
enthesitis-related arthritis (affecting the junctions between tendons and
bones). Using gene expression technology -- a method by which scientists
can determine the relative levels of expression of thousands of different
genes at the same time and compare a pattern from one subject with another
-- the researchers looked for differences in the children's blood samples
that corresponded with the different forms of JIA.

"We analyzed gene expression patterns in blood cells and found that we
could indeed distinguish the major subtypes of JIA," says Dr. Colbert, who
was a leader of this research program at Cincinnati Children's Hospital
Medical Center before coming to NIAMS. "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, M.D., Ph.D., also at
Cincinnati Children's Hospital Medical Center, scientists looked more
closely at patients from the study with one 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, meaning their
blood tested positive for an antibody commonly seen in adults with
rheumatoid arthritis (RA). Surprisingly, the scientists found patterns of
gene expression that indicated at least three subgroups of polyarthritis.
There was an older subgroup (average age 11) 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 (average age 7) 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.

Dr. Colbert says the new findings take pediatric rheumatologists a step
closer to more precisely classifying JIA, and eventually developing
individually tailored treatments that maximize the benefits, while
minimizing the risks. "In pediatric rheumatology, we are at the early
stages of improving our classification system for JIA. 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," he said. "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."

In addition to NIAMS, funding for the studies was provided by the
Cincinnati Children's Hospital Research Foundation and the Arthritis
Foundation Ohio Valley Chapter.

For more information about juvenile arthritis, visit the NIAMS Web site at


<http://www.niams.nih.gov/Health_Info/Juv_Arthritis/default.asp>



For more information about arthritis and rheumatic diseases, visit the
NIAMS Web site at:


<http://www.niams.nih.gov/Health_Info/Arthritis/arthritis_rheumatic_qa.asp>



The mission of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), a part of the Department of Health and Human
Services' National Institutes of Health (NIH), is to support research into
the causes, treatment, and prevention of arthritis and musculoskeletal and
skin diseases; the training of basic and clinical scientists to carry out
this research; and the dissemination of information on research progress
in these diseases. For more information about NIAMS, call the information
clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the
NIAMS Web site at <http://www.niams.nih.gov>.




The National Institutes of Health (NIH) - The Nation's Medical Research
Agency - includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit



<http://www.nih.gov>





The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and its
programs, visit



<http://www.nih.gov>



-----------------------------



REFERENCE:


Barnes M, Grom A, Thompson S, et al.
Subtype-specific peripheral blood gene expression profiles in recent-onset
juvenile idiopathic arthritis
Arthritis Rheum
2009;60(7):2102-2112. DOI 10.1002/art.24601



Griffin T, Barnes M, Ilowite N, et al.
Gene expression signatures in polyarticular juvenile idiopathic arthritis
demonstrate disease heterogeneity and offer a molecular classification of
disease subsets.
Arthritis Rheum
2009;60(7):2113-2123. DOI 10.1002/art.24534




##



This NIH News Release is available online at:
<http://www.nih.gov/news/health/jun2009/niams-29.htm>.




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