Anti-''Saccharomyces cerevisiae'' antibodies (ASCAs) are

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

against antigens presented by the

cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...

of the yeast ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...

''. These antibodies are directed against oligomannose sequences α-1,3 Man (α-1,2 Man α-1,2 Man)_n (n = 1 or 2). ASCAs and perinuclear antineutrophil cytoplasmic antibodies (pANCAs) are the two most useful and often discriminating

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s for

colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) ...

. ASCA tends to recognize Crohn's disease more frequently, whereas pANCA tend to recognize ulcerative colitis. ASCA antibodies react to a yeast protein with mannans, a 200-

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

glycoprotein.

Diseases

Diseases in which ASCA are found include the following: *

Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the e ...

- The association with ASCA is not generally strong, but increased in patients with gastrointestinal symptoms. *

Coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

Colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) ...

Ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...

-familial. **

Microscopic colitis Microscopic colitis refers to two related medical conditions which cause diarrhea: collagenous colitis and lymphocytic colitis. Both conditions are characterized by the presence of chronic non-bloody watery diarrhea, normal appearances on colonosco ...

*** Collagenous colitis *

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

Intestinal yeast and ASCA positive

Intestinal yeast infections are seen in malabsorptive diseases like

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

. In Crohn's disease and ulcerative colitis the presence of intestinal ''S. cerevisiae'' is rare, but the association with irritable bowel in coeliac disease remains unstudied.

Anti-mannans

Mannan (oligomannan) is a component of the yeast

. Antibodies to yeast mannans are found at increased frequency in

and ASCA positive Crohn's tend to have lower low levels of mannan-binding lectin. Experimentally, antibodies to mannans from yeast can also crossreact to mannans of other types of yeast. Study of the sugars indicated that a mannotetraose (4-mer) was responsible for highest response. Studies of the 200 kDa glycoprotein antibodies found them commonly in healthy people, suggesting that the disease associated antibodies are to their carbohydrate moieties. 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. ASCA are serological markers of ''candida albicans'' infections in humans and animals. Mannan-binding lectin ( MBL) is a

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...

produced by humans. In ASCA positive Crohn's disease the serum level of this protein is lower. Cellular response to mannan in ASCA positive peripheral blood lymphocytes could be inhibited by adding MBL, however, a high frequency of mutations in the MBL gene was found in ASCA positive patients. Besides, MBL serum levels were inversely correlated with ASCA levels in Crohn's disease patients with severe clinical phenotypes.

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. 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. This alteration is marked by increased activation markers,

CD25 Interleukin-2 receptor alpha chain (also called CD25) is the human protein encoded by the ''IL2RA'' gene. The interleukin 2 (IL2) receptor alpha (IL2RA) and beta (IL2RB) chains, together with the common gamma chain (IL2RG), constitute the high-a ...

CD69 CD69 (Cluster of Differentiation 69) is a human transmembrane C-Type lectin protein encoded by the gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is ...

, upon proliferative stimulation of T-helper lymphocytes. ASCA positive 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 Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the ''NOD2'' g ...

protein (also known as CARD15) or antibodies to mycoprotein antigen (IgA or IgG), indicating heterogeneous causes for Crohn's disease. Experimental studies show that chemically-induced colitis promotes opportunistic human fungal pathogen ''Candida albicans'' colonization. In turn, ''Candida albicans'' colonization generates ASCA. According to another study, serum samples from patients with invasive candidiasis demonstrated that ASCA levels are significantly elevated compared to healthy controls, but the same, statistically, as of those with Crohn's disease.

References

{{DEFAULTSORT:Anti-Saccharomyces Cerevisiae Antibodies Saccharomyces cerevisiae

Saccharomyces ''Saccharomyces'' is a genus of fungi that includes many species of yeasts. ''Saccharomyces'' is from Greek σάκχαρον (sugar) and μύκης (fungus) and means ''sugar fungus''. Many members of this genus are considered very important in f ...

Food allergies