Pathology Associates Of Lexington, P.A.
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         Anti-Saccharomyces Cerevisiae Antibody Test, - ASCA
      

Tests have been developed to detect IgG and IgA serum antibodies (ASCA) to the cell wall mannin component of the Su 1 strain of this "bakers yeast". The sensitivity (about 50%) is too low for serological screening triage of colitis cases...much less diarrhea of uncertain etiology cases. Is also elevated in 40-60% of celiac disease cases. Therefore not good for differentiating organic from functional colonic disease.

Some have suggested that a combination of ASCA and pANCA testing can add one more piece to the puzzle (an adjunct only8) of discriminating IBD-UC and IBD-CD2,4. The two serologies are of no help in "indeterminate IBD" cases because the vast majority of such cases are still indeterminate after such serological testing3. So, there still is no way to always avoid laparotomy with diagnostic colectomy prior to final pouch surgery for what might finally be proven as IBD-UC. And serologies are of debatible5, 9 help in childhood (way too many negative tests), especially age 5 or younger5. Serology for IgA anti-OmpC (against outer membrane of porin C antigen) and IgG anti-CBir1 (against a bacterial flagellin like antigen associated with the presence of IBD-CD) are used in some additionally atypical scenarios11. P-ANCA (atypical) positive & ASCA positive cases which seem indeterminate may be placed into a colon only IBD-CD if the anti-CBir1 is positive. About half of ASCA neg. IBD-CD are pos. for OmpC13 and may be an IBD-CD group with rapid progression & early need of surgery relative to penetration. Some of IBD-UC cases are positive for the purported IBD-CD marker, IgG/IgA positive ASCA8; but 93% of IBD-CD cases will positive for this pair8 (but, see below). So, correlative serological interpretation is important!

Key ANCA IBD serology interference: about 33% of IBD cases have a low level positive ANA which makes pANCA testing indeterminate...so that pANCA results would be reported "indeterminate"2.

Some other serological markers being mentioned as of early 2009:

  • anti-I-2 (or anti-I2): antibody to a bacterial transcription factor in 19-50% of IBD-CD as with anti-OmpC cases12 (no advantage over OmpC); elevated in celiac disease.
  • antiglycan antibodies (ALCA-penetrating & ACCA-stenosing): in 40% of ASCA neg. IBD-CD cases.
  • PAB (IIF): p[os. in an IBD-CD group

Non-IBD-CD causes of positives (false positives):

  • less than 1% (1 in 163) of normal blood donors are ASCA positive.

    Of 123 cases of primary biliary cirrhosis (PBC), 44% of the AMA negatives were ASCA pos.6

  • of 25 cases of primary sclerosing cholangitis, 53% ASCA pos.6

  • ASCA often elevated in spondyloarthropathies, rheumatoid arthritis

    .
  • 4% of non-IBD cases and 4% of IBD-UC cases have pos. IgG/IgA ASCA combo at Prometheus8.

False negatives:

  • because of high false neg. rate, childhood IBD serology useless5.

  • 23% of IBD-CD are negative for all of the Prometheus IBD panel8.

  • 15% of IBD-UC are negative for all of the Prometheus IBD panel8.

A Possible Use:

While some say that combined elevation of IgG & IgA ASCA is 100% specific for IBD-CD, it is only so for those with unequivocal small bowel involvement7. Serology can't supplant colonoscopy, biopsies, imaging studies and other ancillary studies. But the following may be additive to diagnostic confidence building, if needed & when clinically indicated2:

  1. pANCA elevated...IgG & IgA ASCA not elevated: 91% predictive value for IBD-UC.

  2. pANCA not elevated...IgG & IgA ASCA elevated: 90% predictive value for IBD-CD.

So,maybe it is sometimes worthwhile to get IgG/IgA ASCA serology in those clinically and endoscopically likely to be IBD-CD; and, if they aren't both clearly positive, use an additional measure of caution prior to a final diagnostic declaration of IBD-CD.

References & update sources:

  1. Check W, August 2000 CAP TODAY, The College of American Pathologists web site [CAP]

  2. Mayo Clinic Client Ref. Labs Bulletin #81443

  3. Petras RE (internationally recognized GI pathologist and USA workshop & lecturer), personal e-mail 25 October 2003.

  4. Quinton JF, et. al. (Cedars Sinai GI group), Gut 42:788-91, 1998.

  5. Am. J. Gastroenterolgy 97(8):2005-10, Aug. 2002.

  6. Clin. Exp. Immunol. 132(3):473-6, June 2003.

  7. ARUP Labs on-line test info (a national all-purpose reference lab based in Utah)

  8. Prometheus Laboratories marketing & info bulletin copyright 2002, obtained by one of our team Aug. 2003 (and it contained reprints of Abreu MT, et. al. Use of Serological Tests in Crohn's Disease, Clinical Perspectives in Gastroenterology, May/June 2001 and Dubinsky MC, et. al., Clinical Utility of Serodiagnostic Testing in Suspected Pediatric Infl. Bowel Dis., Am. J. Gastroenterolgy 96[3]:758-765, March 2001.)

  9. Reese GE, et. a., [a meta analysis] "Diagnostic Precision of Anti-Saccharomyces cerevisiae Antibodies and Perinuclear Antineutrophil Cytoplasmic Antibodies in Inflammatory Bowel Disease", Am J Gastroenterol 101:2410–2422, 2006.
  10. Papp M, et. al., "Utility of serological markers in inflammatory bowel diseases:
    Gadget or magic?", World J Gastroenterol 13(14):2028-2036, April 14, 2007.
  11. Lichtenstein GR, "Clinical Focus - Challenges in the Diagnosis of Ulcerative Colitis and Crohn's Disease" [here...discusses some of the Prometheus profile and their unpublished AI diagnostic algorhythm] Medscape website CME "Advances in Inflammatory Bowel Disease, Volume 1", 28 July 2006
  12. Joosens S, et. al., "Anti-outer membrane of porin C and anti-I2 antibodies in indeterminate colitis", Gut, 55:1667-1669, 2006.
  13. Jaskowski TD, et. al., "Analysis of Serum Antibodies in Patients Suspected of Having Inflammatory Bowel Disease", Clinical and Vaccine Immunology,13(6):655-660, June 2006.
(posted 31 July 2003; latest update 30 January 2009)
 
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