Nov. 19, 2009 -- Rare genetic mutations may trigger inflammatory bowel
disease (IBD) in young children.
A new study shows genetic mutations affecting the interleukin-10 receptor
are associated with severe early-onset IBD in children; a stem cell transplant
was successful in putting the disease into remission in one child affected by
"Our study provides an example of the power of molecular medicine to go from
the bedside (for diagnosis) to the bench (for the discovery of mutations) and
back to the bedside (for treatment)," write researcher Erik-Oliver Glocker, MD,
of the Royal Free Hospital and University College London, and colleagues in the
New England Journal of Medicine.
Inflammatory bowel disease affects about 2 million children and adults in
the U.S. The disease results in inflammation of the gastrointestinal lining,
causing damage and ulcerations. IBD includes Crohn's disease, which affects any
part of the gastrointestinal (GI) tract, and ulcerative colitis, which is
limited to the large intestine.
In the study, researchers screened genetic samples from two unrelated
families with children affected by childhood IBD and six additional children
with early-onset colitis for mutations in the interleukin-10 receptor
They found three distinct genetic mutations in four of nine patients with
early-onset colitis. The mutations interfered with the formation of the
interleukin-10 receptor. Interleukin-10 keeps excessive inflammation in check.
Without adequate interleukin-10 receptors, the body can't use interleukin-10 in
the way it should.
One affected child was treated with stem cell transplantation and
experienced a complete remission of the disease.
Researchers say interleukin receptors are found on many cells in both the
non-immune and immune system, and further studies are needed to determine which
types of cells are primarily responsible for the inflammation associated with
inflammatory bowel disease.
Another study released earlier this week also demonstrated a link between
the interleukin gene and childhood IBD. Experts say the new findings should
stimulate further research into genetic therapies for the disease.
"This study should spur new energy to fuel the search for genetic and
functional contributions by interleukin-10 ... in understanding the pathogenesis
of inflammatory bowel disease and to reevaluate therapeutic strategies," writes
Brian Kelsall, MD, of the National Institutes of Health, in an editorial that
accompanies the study.