Anti–Saccharomyces cerevisiae antibody

Anti-Saccharomyces cerevisiae antibodies (ASCAs) are antibodies against antigens presented by the cell wall of the yeast Saccharomyces cerevisiae. ASCAs and perinuclear antineutrophil cytoplasmic antibodies (pANCAs) are the two most useful and often discriminating biomarkers for colitis.[1] ASCA tends to recognize Crohn's disease more frequently, whereas pANCA tend to recognize ulcerative colitis.[2]

Antibody(s)
Anti-saccharomyces cerevisiae
Antigen
Isoform		Mannans
Antigen SourceSaccharomyces cerevisiae
Antigen genepro
Affected organ(s)Large Intestine
Affected
tissue(s)		Epithelium
Associated
Disease(s)		Colitis

ASCA antibodies react to a yeast protein with mannans,[3] a 200-kDa glycoprotein.[4] Diseases in which ASCA are found include the following:

Yeast S. cerevisiae, the cells are bordered by cell wall that contains the antigen for ASCA

Intestinal yeast and ASCA+. Intestinal yeast infections are seen in malabsorptive diseases like coeliac disease. In Crohn's disease and ulcerative colitis the presence of intestinal S. cerevisiae is rare, but the association with irritiable bowel in coeliac disease remains unstudied.[13]

Anti-mannans
A photomicrograph of Candida albicans showing hyphal outgrowth and other morphological characteristics.

Mannan (oligomannan) is a component of the yeast cell wall. Antibodies to yeast mannans are found at increased frequency in Crohn's disease and ASCA+ Crohn's tend to have lower low levels of mannan-binding lectin.[14] Experimentally, antibodies to mannans from yeast can also crossreact to mannans of other types of yeast.[15] Study of the sugars indicated that a mannotetraose (4-mer) was responsible for highest response. [16] Studies of the 200 kDa glycoprotein antibodies found them commonly in healthy people, suggesting that the disease associated antibodies are to their carbohydrate moieties.[17] Mannans from other yeast, for example candida albicans, have found to cross react with ASCA which suggests that other yeast may induce ASCA associated diseases.

Mannan-binding lectin (MBL) is a lectin produced by humans. In ASCA+ Crohn's disease the serum level of this protein is lower. Cellular response to mannan in ASCA+ peripheral blood lymphocytes could be inhibited by adding MBL, however, a high frequency of mutations in the MBL gene was found in ASCA+ patients.[18] Besides, MBL serum levels were inversely correlated with ASCA levels in Crohn’s disease patients with severe clinical phenotypes.[19]

Crohn's disease

ASCA are consistently higher in frequency in Crohn's disease. Yeast cause a three-fold increase in lymphocyte proliferation relative to normal controls.[20] The ASCA antibodies are also more frequently found in familial Crohn's disease.[9] An altered humoral and cellular response to mannan is observed and may be due to a loss of yeast tolerance.[21] This alteration is marked by increased activation markers, CD25/CD69, upon proliferative stimulation of T-helper lymphocytes. ASCA+ is a predictor for Crohn's disease with high specificity and positive predictive value (87% and 78% respectively).[22] ASCA are associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0.001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years (P < 0.0001). There is no association between genetic markers for Crohn's disease and NOD2/CARD15 or MP (IgA or IgG) indicating heterogeneous causes for Crohn's disease.[23] Experimental studies show that chemically-induced colitis promotes opportunistic human fungal pathogen Candida albicans colonization. In turn, Candida albicans colonization generates ASCA.[24]

References
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  2. Joossens S, Reinisch W, Vermeire S, et al. (2002). "The value of serologic markers in indeterminate colitis: a prospective follow-up study". Gastroenterology. 122 (5): 1242–1247. doi:10.1053/gast.2002.32980. PMID 11984510.
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  14. Seibold F, Boldt AB, Seibold-Schmid B, et al. (2007). "Association of deficiency for mannan-binding lectin with anti-mannan antibodies in Crohn's disease: A family study". Inflamm. Bowel Dis. 13 (9): 1077–1082. doi:10.1002/ibd.20156. PMID 17480019.
  15. Schaffer T, Müller S, Flogerzi B, Seibold-Schmid B, Schoepfer AM, Seibold F (2007). "Anti-Saccharomyces cerevisiae mannan antibodies (ASCA) of Crohn's patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans". Inflammatory Bowel Diseases. 13 (11): 1339–1346. doi:10.1002/ibd.20228. PMID 17636567.
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  19. Choteau Laura; Vasseur Francis; Lepretre Frederic; Figeac Martin; Gower-Rousseau Corine; Dubuquoy Laurent; Poulain Daniel; Colombel Jean-Frederic; Sendid Boualem; Jawhara Samir (2016). "Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients". Scientific Reports. 6 (1): 29636. doi:10.1038/srep29636. ISSN 2045-2322. PMC 4940739. PMID 27404661.
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  22. [citation needed]
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  24. Jawhara Samir; Thuru Xavier; Standaert‐Vitse Annie; Jouault Thierry; Mordon Serge; Sendid Boualem; Desreumaux Pierre; Poulain Daniel (April 2008). "Colonization of Mice byCandida albicansIs Promoted by Chemically Induced Colitis and Augments Inflammatory Responses through Galectin‐3". The Journal of Infectious Diseases. 197 (7): 972–980. doi:10.1086/528990. ISSN 0022-1899. PMID 18419533.
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