title: Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn's patients and are not inducible in murine models of colitis.
abstract: OBJECTIVE
  To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology.
  
  
  METHODS
  Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (Delta IgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure.
  
  
  RESULTS
  ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the Delta IgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or Delta IgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014).
  
  
  CONCLUSIONS
  The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.
authors.affiliation: Division of Gastroenterology, Department of Clinical Research, University Hospital Bern. stefan.mueller@dkf.unibe.ch
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.forename: Maya
authors.initials: M
authors.lastname: Styner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Seibold-Schmid
authors.forename: Beatrice
authors.initials: B
authors.lastname: Flogerzi
authors.forename: Michael
authors.initials: M
authors.lastname: Mähler
authors.forename: Astrid
authors.initials: A
authors.lastname: Konrad
authors.forename: Frank
authors.initials: F
authors.lastname: Seibold
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood* / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D003092:Colitis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008875:Middle Aged; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D013997:Time Factors
chemical_list: D000908:Antibodies, Fungal; D016753:Interleukin-10; D002097:C-Reactive Protein