IBD Update

Posted by Elaine Moore Jun 24, 2006

Inflammatory bowel disease (IBD) is a collective term encompassing Crohn's disease and ulcerative colitis. These disorders lead to gastrointestinal distress pain and inflammation, and they can lead to the development of fistulas. These two autoimmune disorders collectively affect about one in every one thousand persons, and recent studies indicate that this number is on the rise. Like other autoimmune disorders, IBD is associated with both genetic and environmental factors that influence disease susceptibility, progression, and the variability seen in symptoms and their severity.

IBD usually emerges in people from ages 10 through 20 or who are in their early 30s. Although mortality is low, IBD can cause significant episodes of disease activity with the potential to cause frequent hospital admissions, chronic ill health, persistent infections, altered development, poor quality of life, and a decreased sense of social assuredness. The greatest chance for complications and related development problems occurs in the youngest patients, for whom developmental problems are common. For many years, advances in IBD diagnosis and treatment have been lacking. However, the tide has turned and recent advances in inflammatory bowel disease (IBD) include the development of molecular based diagnostic tests and emerging biologic treatments.

Molecular genetics testing shows that people with IBD have distinct genetic markers, with independently replicated loci designated as IBD1 through IBD5. Furthermore, genetic studies show that ulcerative colitis and Crohn's disease share some but not all of a limited set of disease susceptibility genes. From a genetic standpoint, IBD stands alone among complex genetic diseases because of these 5 confirmed susceptibility loci. And in recent years the responsible gene for IBD, NOD2, has been located on chromosome 16. This gene highly suggests that a defective immune response to enteric bacteria is the underlying cause of IBD. Specifically, the immune system in patients with IBD fails to respond properly to the lipopolysaccharides of enteric bacteria.

Hereditary European studies show that IBD is much more likely to develop in families with a history of IBD, especially when a first-degree or second-degree relative is affected. Between 6-32 percent of patients with IBD have a first or second-degree relative with IBD, with a greater association seen in Crohn's disease. A strong familial association also influences age of onset, disease location, extra-intestinal (other than gastrointestinal) symptoms, and fistulizing pathology (tendency to form fistulas). The degree of genetic contribution to IBD also follows ethnic lines. For instance, studies show that Jewish patients in both Cleveland and Los Angeles had a higher likelihood of developing IBD than non-Jewish patients in these locales. Studies also suggest that immune system genes, for instance the tumor necrosis factor-alpha gene also influence disease development and progression. Overall, genetic susceptibility appears to be the greatest risk factor for developing IBD.

Various environmental agents have been found to trigger IBD development. These include: antibiotics, analgesics such as aspirin and ibuprofen, gastrointestinal infection with various viruses and bacteria, including Klebsiella and Yesina, and toxic proteins in wheat, rye, and barley. Gluten sensitivity is also thought to be a contributing factor in the development of IBD. Smoking has also been found to influence IBD development, with IBD being twice as likely to be found in smokers.

Studies of animal models with symptoms of IBD have provided valuable clues regarding disease progression. For instance, immune system chemicals known as cytokines released during the misdirected immune response contribute to the chronic inflammation seen in patients with IBD. These studies have led to various treatments. For example, infliximab (Remicade) was introduced as a treatment to reduce levels of inflammatory cytokines such as tumor necrosis factor-alpha. However, about one-third of patients with IBD do not respond favorably to infliximab. Various ongoing studies focusing on the immune mechanism in IBD development will undoubtedly provide further insights into effective treatment modalities.

Resource:

Eric Staros, Inflammatory Bowel Disease: A Genomic Picture Predicts a Changing Response from the Laboratory, Laboratory Medicine, April 2004.