Wednesday, June 26, 2013

Blood Tests for Colitis and Crohn's Disease: an Introduction


Blood tests for colitis and Crohn's disease are a relatively new and exciting development that have added significantly to the screening, diagnosis and management of ulcerative colitis and Crohn's disease. Differentiating the two may allow better predictions regarding responses to medical treatments, decisions regarding surgery options and the risks of various complications. Antibodies to various proteins including Baker's or Brewer's yeast (saccharomyces cerevisiae) and bacteria like Escherichia. coli (E. coli) are present in the blood of many people with Crohn's disease but rarely in normal people. Antibodies to a normal cell component, a nuclear protein, is present in most people with ulcerative colitis, a few people with Crohn's whose colitis behaves more like ulcerative colitis than Crohn's, and rarely in normal people.

Antibody tests or serologic markers are blood tests looking for markers of diseases. The serologic markers or antibody tests for ulcerative colitis and Crohn's disease are pANCA and ASCA, OmpC, and CBir1 Flagelin respectively. The latter three blood tests for Crohn's are only available through one laboratory, Prometheus Laboratories, Inc.

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) of unknown cause that only involves the colon. It affects the superficial lining of the colon and rarely causes bowel obstruction (blockage) or perforation (rupture) but frequently causes severe bloody diarrhea, blood in the stool, weight loss, abdominal pain, as well as joint aches or arthritis, skin rashes, eye irritation and occasionally a severe liver disorder known as primary sclerosing cholangitis that can lead to cirrhosis and liver cancer. Ulcerative colitis can be cured by complete removal of the colon but not Crohn's disease.

Crohn's disease can also cause colitis but usually also affects the very end of the small intestine called the ileum (ileitis or regional enteritis). When Crohn's affects only the colon it may be difficult to distinguish it from ulcerative colitis though Crohn's tends to affect the colon in a patchy manner whereas ulcerative colitis is continuous. Crohn's can affect the gastrointestinal tract anywhere from the mouth to the anus and is not curable by removing the colon. It is also frequently associated with bowel strictures (constrictions) causing obstruction that may require surgery. It also may be associated with fistula that are abnormal connections of the intestine to other organs and the skin or it can result in abscesses or perforation requiring surgery It is important to distinguish Crohn's disease from ulcerative colitis since medical treatments and surgical approaches may differ and the types of complications that can occur can be much different.

Traditionally, the diagnosis of ulcerative colitis and Crohn's disease is highly accurate by the appearance of the colon on colonoscopy or x-rays that confirm the presence or absence of involvement of other parts of the intestinal tract. Diagnosis is confirmed by a typical pattern of inflammation of the intestine lining as seen under the microscope on tissue obtained by biopsy during colonoscopy. However, before blood tests were available about 10% of people with IBD were diagnosed as having an indeterminate colitis because the biopsies could not distinguish between the ulcerative colitis and Crohn's disease.

The blood tests currently available are pANCA, anti-ASCA, anti-OmpC, and anti-CBir1 flagelin antibodies. pANCA is the peripheral anti-nuclear antibody. It is an abnormal antibody to nuclear protein of cells and is highly sensitive and specific for ulcerative colitis. The pANCA anbibody has been further divided into subsets by Prometheus Laboratories Inc. Neutrophil-specific pANCA ELISA (NSNA) is positive in the majority of people with ulcerative colitis (UC) and a small subset of people with Crohn's disease that have disease characteristics more like UC. Immunofluorescent cellular staining of neutrophils (NSNA IFA) and enzyme Dnase testing (NSNA DNase sensitivity) is also done as part of the Prometheus IBD Serology 7. The latter test when present in high levels is significantly associated with development of inflammation of the rectal pouch (pouchitis) created when someone has their entire colon removed for ulcerative colitis that does not respond to medical treatment.

ASCA is anti-saccharomyces cerevisiae antibody. Saccharomyces cerevisiae is Brewer's or Baker's yeast. Crohn's patients have a high prevalence of abnormal antibodies to this yeast. Some have suggested that another yeast, Candida albicans, somehow plays a role in this abnormal response. A few people with celiac disease have this antibody present in their blood in the absence of signs of Crohn's disease. OmpC is the abbreviation for an antibody that develops in many Crohn's patients to the outer membrane porin protein of the bacteria E. coli though that bacteria is not thought to be the cause of Crohn's disease. Just recently Prometheus Laboratories added antibody testing for a specific protein on bacteria that constitutes the flagelin or hair like structure on certain bacteria enabling movement and attachment of bacteria in the intestine called CBir1 flagelin.

Future blood tests may include antibodies against certain sugar (mannose) residues in the cell wall of the yeast saccharomyces cerevisiae. Anti-laminaribioside and anti-chitobioside antibodies were recently reported to be present in Crohn's patients who were anti-ASCA negative possibly further strengthening the ability to distinguish them from people with ulcerative colitis. This is also interesting because of suspicions and the lay public interest in the role of sugars or glycans and yeast in IBD. In particular the reports in lay literature of success of carbohydrate specific diet in IBD.

If you have a diagnosis of ulcerative colitis or Crohn's disease these blood tests may be very helpful in your treatment. If you have unexplained abdominal pain, diarrhea, or blood in your stools then these tests should be considered. If you have a diagnosis of irritable bowel syndrome, these tests may exclude ulcerative colitis and Crohn's disease. Since as many as 10% of people with ulcerative colitis and Crohn's disease may also have celiac disease, celiac blood tests should also be considered. Lactose intolerance is also common in IBD, IBS and celiac disease.

Future helpful information on colitis, Crohn's disease, celiac disease, food allergies, food intolerance, food sensitivity, eosinophilic esophagitis and irritable bowel syndrome will be available from Dr. Scot Lewey, the food allergy expert-the food doc at http://www.thefooddoc.com. Information on colitis and Crohn's disease can also be obtained from the Crohn's and Colitis Foundation of America (CCFA, http://www.ccfa.org). Dr. Scot Lewey is a member of the medical advisory panel for the Rocky Mountain Chapter of CCFA. For more information about Prometheus Laboratories Inc. see http://www.prometheuslabs.com. A more detailed explanation of the blood tests can be found in a separate article by the food doc and references below.

Abreu MT et.al. Use of Serologic Tests in Crohn's Disease. Clinical Gastroenterology and Hepatology. Vol.4, No. 3. 2001

Dotan I et.al. Antibodies Against Laminaribioside and Chitiobioside Are Novel Serologic Markers in Crohn's Disease. Gastroenterology. Vol.131, No. 2. 2006

Mei, L et.al. Familial Expression of Anti-Escherichia coli Outer Membrane Porin C in Relatives of Patients with Crohn's Disease. Gastroenterology. Vol. 130, No. 4 2006

Stadaert-Vitse et.al. Candida albicans Is an Immunogen for Anti-Saccharomyces cerevisiae Antibody Markers of Crohn's Disease. Gastroenterology. Vol 130, No. 6. 2006

Targan, SR et.al. Antibodies to Cbir1 Flagelin Define a Unique Response That Is Associated Independently Crohn's Disease. Gastroenterology. Vol.128, No.7. 2005

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