Immune mechanisms and natural history of inflammatory bowel disease

Abstract

The gastrointestinal tract uses a system of tolerance and
controlled inflammation to limit the response to dietary or
bacteria-derived antigens in the gut. The triggering factor
for this and cascade whether it represents an auto-antigen
or an heteroantigen is still to be elucidated. It has been
also demonstrated that a serologic anti-microbial response
in CD patients exists. This response includes antibodies
against saccharomyces cerevisiae (ASCA), E.coli outer
membrane porin C (Omp-C), flagelin (cBir1) and pseudomonas
aeroginosa (l2). Host response to microbial pathogens
includes self-defense mechanisms such as defensins,
pattern recognition receptors (PRRs) and TLRs (Toll Like
Receptors).
Natural history of IBD has been described mainly through
studies in American and north European IBD cohorts. In
general, 50-60% of IBD patients are in remission during
any given year. The likelihood of steroid dependency remains
high in IBD. The prediction of disease location seems
quite safe as the location of the disease remains stable over
time. By contrast the disease behaviour changes over time
with increasing risk for structuring/penetrating disease with
longer disease duration. The question whether currently
available therapies are able to alter natural history of IBD
still remains unanswered. The risk of colorectal cancer in
UC patients begins to increase 8 years from diagnosis and
high risk groups are patients with extensive colitis, young
age at UC onset, familial cancer history and co-existing primary sclerosing cholangitis. In CD the risk of cancer
seems to be comparatively smaller. Life expectancy of CD
patients is slightly lower compared to healthy subjects while
life expectancy in UC patients is generally normal.