Serum markers can be used to identify patients with ulcerative colitis most likely to have inflammatory complications after ileal pouch–anal anastomosis (IPAA), according to the May issue of Clinical Gastroenterology and Hepatology.
More than 20% of individuals with ulcerative colitis eventually need surgery for this disease. Patients with fulminant or chronic treatment-refractory ulcerative colitis and colonic dysplasia undergo colectomy with ileal pouch–anal anastomosis (IPAA). Despite the surgical removal of the colon, inflammation of the ileal reservoir (pouchitis) occurs in 12%–50% of patients, and is a challenge to treat. Some patients with pouchitis go on to develop Crohn’s disease-like features of the pouch, characterized by inflammation in the afferent limb, proximal small bowel strictures unrelated to surgery, or perianal or abdominal fistulas or abscesses long after the IPAA procedure.
There are several factors that contribute to inflammatory complications of the ileal pouch, such as smoking and primary sclerosing cholangitis. But better markers are needed to identify which patients undergoing the IPAA procedure are most likely to develop pouchitis.
Several serum markers have been used to classify patients with ulcerative colitis and could be associated with pouchitis. Some of these are antibodies against components of the enteric microflora. Markers include atypical perinuclear antineutrophil cytoplasmic antibodies (pANCAs), anti-Saccharomyces cerevisiae antibody (ASCA), an antibody against outer membrane porin C (Omp C), the I2 antibody, and anti-CBir1 flagellin.
Andrea Tyler et al. investigated whether these markers, and other factors, were associated with outcomes of 420 patients with ulcerative colitis who underwent colectomy with IPAA. Of these subjects, 70.7% did not develop pouchitis, 16.8% developed chronic pouchitis, and 12.5% developed the Crohn’s disease-like phenotype.
As expected, Tyler et al. found that current or ex-smokers were significantly more likely to develop Crohn’s disease-like features of the pouch than non-smokers.
In serum samples, the antibodies anti-CBir1 or ASCA IgG were associated with chronic pouchitis and the Crohn’s disease-like features (see figure).
Among patients that developed the Crohn’s disease-like outcome, 53.5% and 14.0% tested positive for anti-CBir1 and ASCA IgG, respectively, compared with 21.4% and 3.8% in the group that did not develop pouchitis and 28.3% and 5.0% of those with chronic pouchitis.
Furthermore, the more antibody markers detected, the greater the likelihood of developing a Crohn’s disease-like phenotype of the pouch.
Ulcerative colitis has been proposed to be caused, in part, by increased intestinal permeability to microbial antigens—these induce an adaptive immune response that includes production of antimicrobial antibodies. After surgery, individuals with a strong immune response might be more sensitive to changes in the microflora of the pouch, resulting in changes in antimicrobial antibody titers and pouch inflammation.
The findings of Tyler et al. support previous studies showing that the stronger the adaptive immune response in patients with ulcerative colitis, the higher the likelihood of pouch inflammatory complications after colectomy with IPAA.
In an editorial that accompanies the article, Konstantinos A. Papadakis says that we should intensify medical therapy for patients with ulcerative or even inderminant colitis who have a strong adaptive immune response, to prevent inflammatory pouch complications. Patients might be given preventive treatment after IPAA, such as probiotics or even immunomodulators, but further studies are needed.
Papadakis adds that it is important to study patients who develop inflammatory complications following IPAA, to learn more about changes in the microbiome of the pouch and their effect on the immune response in different individuals.
Identification of serum markers to predict the severity and potential complications from IPAA could allow clinicians to optimize treatment and implement measures to prevent inflammation.
Read the article online.
Tyler AD , Milgrom R , Xu W , et al. Antimicrobial antibodies are associated with a Crohn’s disease-like phenotype following ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 2012;10:507–512.e1.
Read the accompanying editorial.
Papadakis KA. Predicting outcomes after restorative proctocolectomy for ulcerative colitis. Clin Gastroenterol Hepatol 2012;10:447–449.