title: Increased titers of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients with reduced H-ficolin levels but normal MASP-2 activity.
abstract: OBJECTIVE
  Mannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA.
  
  
  METHODS
  ASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA.
  
  
  RESULTS
  In CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p<0.001 and p=0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p=0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p=0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients.
  
  
  CONCLUSIONS
  Our results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development.
authors.affiliation: Department of Clinical Research, Division of Gastroenterology, University Hospital Bern, University of Bern, Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schaffer
authors.forename: Beatrice
authors.initials: B
authors.lastname: Flogerzi
authors.forename: Alain M
authors.initials: AM
authors.lastname: Schoepfer
authors.forename: Frank
authors.initials: F
authors.lastname: Seibold
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal / Q000097:blood*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000201:enzymology; D003424:Crohn Disease / Q000097:blood* / Q000201:enzymology; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D008875:Middle Aged; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000908:Antibodies, Fungal; C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases