"When the digestive immune system's counter-attack is insufficient to clear the threat," Ms. Villani continued, "there is a bacterial infiltration in the intestinal wall through the first line of defense mechanisms.
The digestive immune system will again try to repel the threat, but the effort may not be sufficient, and this usually leads to a vicious cycle that results in chronic inflammation in the intestinal wall. And that is Crohn's Disease."
"This gene also plays a central role in the regulation of fever, which is one of the most primitive defense mechanisms that exists in humans to fight the surrounding pathogenic bacteria," Dr. Hudson added.
"DNA sequence variations in the NLRP3 gene are also known to be responsible for hereditary periodic fever syndromes."
"Previously published genome-wide association studies have already detected more than 30 distinct Crohns Disease genetic factors, but these only explain about one-fifth of Crohn's Disease heritability", said Dr. Franchimont.
Though these results will not lead to any new short-term treatments for Crohn's Disease, Dr. Franchimont is confident that in the longer term it will benefit crohns patients' care.
"Studies like this one give us a better understanding of key pathways and pathogenic mechanisms involved in Crohn's Disease," he said. "Now that we are aware of the role of bacterial sensors in the disease, steps can be taken to develop a new treatment strategy."
The Crohns study was supported by grants from the Canada Foundation for Innovation, the Canada Research Chair program, the Research Institute of the McGill University Health Centre and the Crohn's & Colitis Foundation of Canada (CCFC).
The study was led by McGill PhD candidate Alexandra-Chloé Villani under the supervision of Dr. Denis Franchimont and Dr. Thomas Hudson. Dr. Franchimont, now with the Erasme Hospital in Brussels, Belgium, was a Canada Research Chair formerly affiliated with the Gastroenterology Dept. of the MUHC.
Dr. Hudson, former Director of the McGill University and Génome Québec Innovation Centre, is now the President and Scientific Director of the Ontario Institute for Cancer Research (OICR), located in Toronto.
More about Crohn's Disease
Crohn's Disease, a chronic relapsing inflammatory disease of the digestive system, can affect any part of the gastrointestinal tract. Crohns Disease sufferers exhibit a number of different symptoms in various combinations. These include
- abdominal pain,
- bloody diarrhea,
- vomiting and
- weight loss.
Rarer complications of Crohns Disease include skin manifestations, arthritis and eye inflammation.
Crohn's disease is found throughout the world.
It is most common in North America, Northern Europe, and Canada. Crohns Disease affects between 400,000 and 600,000 people in North America.
ScienceDaily (Jan. 10, 2009) — Adapted from materials provided by McGill University, via EurekAlert!, a service of AAAS.