Anti-saccharomyces cerevisiae antibodies

AbBox
Antigen = saccharomyces cerevisiae
OneIsoform = yes
OneIsoformSpecialName = Mannins
OneSource = "Saccharomyces cerevisiae"
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OneOrgan = Large Intestine
OneTissue = Epithelium
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OneDisease = Colitis
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Anti-"Saccharomyces cerevisiae" antibodies (ASCA), along with perinuclear antineutrophil cytoplasmic antibodies (pANCA), are among the two most useful and often discriminating markers for colitis.cite journal | author = Desplat-Jégo S, Johanet C, Escande A, "et al" | title = Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: results of a multicenter study | journal = World J. Gastroenterol. | volume = 13 | issue = 16 | pages = 2312–8 | year = 2007 | pmid = 17511029 | doi = ] ASCA tends to recognize Crohn's disease more frequently, whereas pANCA tend to recognize ulcerative colitis.cite journal | author = Joossens S, Reinisch W, Vermeire S, "et al" | title = The value of serologic markers in indeterminate colitis: a prospective follow-up study | journal = Gastroenterology | volume = 122 | issue = 5 | pages = 1242–7 | year = 2002 | pmid = 11984510 | doi = ]

ASCA antibodies react to the following yeast proteins
* Mannanscite journal | author = Lindberg E, Magnusson KE, Tysk C, Järnerot G | title = Antibody (IgG, IgA, and IgM) to baker's yeast (Saccharomyces cerevisiae), yeast mannan, gliadin, ovalbumin and betalactoglobulin in monozygotic twins with inflammatory bowel disease | journal = Gut | volume = 33 | issue = 7 | pages = 909–13 | year = 1992 | pmid = 1644330 | doi = ]
** 200 kDA glycoprotein.cite journal | author = Heelan BT, Allan S, Barnes RM | title = Identification of a 200-kDa glycoprotein antigen of Saccharomyces cerevisiae | journal = Immunol. Lett. | volume = 28 | issue = 3 | pages = 181–5 | year = 1991 | pmid = 1885214 | doi = ] Diseases in which ASCA are found:
* Behçet's diseasecite journal | author = Monselise A, Weinberger A, Monselise Y, Fraser A, Sulkes J, Krause I | title = Anti-Saccharomyces cerevisiae antibodies in Behçet's disease--a familial study | journal = Clin. Exp. Rheumatol. | volume = 24 | issue = 5 Suppl 42 | pages = S87–90 | year = 2006 | pmid = 17067434 | doi = ] - The association with ASCA is not generally strong, but increased in patients with gastrointestinal symptoms.cite journal | author = Fresko I, Ugurlu S, Ozbakir F, "et al" | title = Anti-Saccharomyces cerevisiae antibodies (ASCA) in Behçet's syndrome | journal = Clin. Exp. Rheumatol. | volume = 23 | issue = 4 Suppl 38 | pages = S67–70 | year = 2005 | pmid = 16273768 | doi = ]
*Celiac diseasecite journal | author = Giaffer MH, Clark A, Holdsworth CD | title = Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their possible pathogenic importance | journal = Gut | volume = 33 | issue = 8 | pages = 1071–5 | year = 1992 | pmid = 1398231 | doi = ] cite journal | author = Toumi D, Mankaï A, Belhadj R, Ghedira-Besbes L, Jeddi M, Ghedira I | title = Anti-Saccharomyces cerevisiae antibodies in coeliac disease | journal = Scand. J. Gastroenterol. | volume = 42 | issue = 7 | pages = 821–6 | year = 2007 | pmid = 17558905 | doi = 10.1080/00365520601154996]
* Colitis
** Ulcerative colitis-familial.cite journal | author = Annese V, Andreoli A, Andriulli A, "et al" | title = Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study | journal = Am. J. Gastroenterol. | volume = 96 | issue = 8 | pages = 2407–12 | year = 2001 | pmid = 11513182 | doi = ]
** Microscopic colitis
*** Collagenous colitiscite journal | author = Holstein A, Burmeister J, Plaschke A, Rosemeier D, Widjaja A, Egberts EH | title = Autoantibody profiles in microscopic colitis | journal = J. Gastroenterol. Hepatol. | volume = 21 | issue = 6 | pages = 1016–20 | year = 2006 | pmid = 16724988 | doi = 10.1111/j.1440-1746.2005.04027.x]
*Crohn's diseasecite journal | author = Main J, McKenzie H, Yeaman GR, "et al" | title = Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease | journal = BMJ | volume = 297 | issue = 6656 | pages = 1105–6 | year = 1988 | pmid = 3143445 | doi = ] cite journal | author = Barnes RM, Allan S, Taylor-Robinson CH, Finn R, Johnson PM | title = Serum antibodies reactive with Saccharomyces cerevisiae in inflammatory bowel disease: is IgA antibody a marker for Crohn's disease? | journal = Int. Arch. Allergy Appl. Immunol. | volume = 92 | issue = 1 | pages = 9–15 | year = 1990 | pmid = 2246081 | doi = ]

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.cite journal | author = Mallant-Hent RC, Mooij M, von Blomberg BM, Linskens RK, van Bodegraven AA, Savelkoul PH | title = Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti-Saccharomyces cerevisiae antibodies in serum of patients with IBD | journal = World J. Gastroenterol. | volume = 12 | issue = 2 | pages = 292–7 | year = 2006 | pmid = 16482632 | doi = ]

=Anti-mannans=
Mannan (oligomannin) 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.cite journal | author = Seibold F, Boldt AB, Seibold-Schmid B, "et al" | title = Association of deficiency for mannan-binding lectin with anti-mannan antibodies in Crohn's disease: A family study | journal = Inflamm. Bowel Dis. | volume = 13 | issue = 9 | pages = 1077–82 | year = 2007 | pmid = 17480019 | doi = 10.1002/ibd.20156] Experimentally, antibodies to mannans from yeast can also crossreact to mannans of other types of yeast.cite journal | author = Schaffer T, Müller S, Flogerzi B, Seibold-Schmid B, Schoepfer AM, Seibold F | title = 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 | journal = | volume = | issue = | pages = | year = 2007 | pmid = 17636567 | doi = 10.1002/ibd.20228] Study of the sugars indicated that a mannotetraose (4-mer) was responsible for highest response.cite journal | author = Sendid B, Colombel JF, Jacquinot PM, "et al" | title = Specific antibody response to oligomannosidic epitopes in Crohn's disease | journal = Clin. Diagn. Lab. Immunol. | volume = 3 | issue = 2 | pages = 219–26 | year = 1996 | pmid = 8991640 | doi = ] Studies of the 200 kDaglycoprotein antibodies found them commonly in healthy people, suggesting that thedisease associated antibodies are to their carbohydrate moieties. cite journal | author = Sander U, Kunze I, Bröker M, Kunze G | title = Humoral immune response to a 200-kDa glycoprotein antigen of Saccharomyces cerevisiae is common in man | journal = Immunol. Lett. | volume = 61 | issue = 2-3 | pages = 113–7 | year = 1998 | pmid = 9657263 | doi = ] 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.cite journal | author = Seibold F, Konrad A, Flogerzi B, "et al" | title = Genetic variants of the mannan-binding lectin are associated with immune reactivity to mannans in Crohn's disease | journal = Gastroenterology | volume = 127 | issue = 4 | pages = 1076–84 | year = 2004 | pmid = 15480986 | doi = ]

=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.cite journal | author = Young CA, Sonnenberg A, Burns EA | title = Lymphocyte proliferation response to baker's yeast in Crohn's disease | journal = Digestion | volume = 55 | issue = 1 | pages = 40–3 | year = 1994 | pmid = 8112496 | doi = ] The ASCA antibodies are also more frequently found in familial Crohn's disease. An altered humoral and cellular response to mannan is observed and may be due to a loss of yeast tolerance.cite journal | author = Konrad A, Rütten C, Flogerzi B, Styner M, Göke B, Seibold F | title = Immune sensitization to yeast antigens in ASCA-positive patients with Crohn's disease | journal = Inflamm. Bowel Dis. | volume = 10 | issue = 2 | pages = 97–105 | year = 2004 | pmid = 15168808 | doi = ] 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). 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 diseasecite journal | author = Walker LJ, Aldhous MC, Drummond HE, "et al" | title = Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease are associated with disease severity but not NOD2/CARD15 mutations | journal = Clin. Exp. Immunol. | volume = 135 | issue = 3 | pages = 490–6 | year = 2004 | pmid = 15008984 | doi = ] . [Note: "CD" is a common abbreviation for Crohn's disease. It is more commonly used for coeliac disease which may be primary to some forms of colitis. When reviewing abstracts for colitis, it is important to note the abbreviation is used for both.]

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