title: The lectin pathway of the complement system is downregulated in Crohn's disease patients who respond to anti-TNF-α therapy.
abstract: OBJECTIVE
  The lectin pathway of the complement system is initiated through the recognition of pathogens or altered self-structures by mannan-binding lectin (MBL) or ficolins and subsequent activation of MBL-associated serine proteases (MASPs). Altered ficolin levels may contribute to a dysregulated immune response in Crohn's disease (CD). A complete analysis of the lectin pathway has not been performed in patients with CD. We hypothesised that the lectin pathway proteins exacerbate inflammation in CD.
  
  
  METHODS
  We assessed the lectin pathway proteins in 43 patients with active CD & 350 blood donors by measuring the serum levels of MBL; M-, H-, and L-ficolin; MASP-2; MASP-3; and MAp44. In patients with CD, the blood samples were obtained during induction treatment with infliximab or adalimumab.
  
  
  RESULTS
  Of 43 patients with CD, 32 (74%) were classified as responders. We observed a nearly 50% decrease in median M-ficolin levels between day 0 and weeks 1/7 in the responders (p<0.001), whereas there was no decrease in the non-responders. MASP-2 levels decreased from baseline to week 1 in both the responders (37%, p<0.0001) and the non-responders (29%, p=0.02). In the responders only, the level of the inhibitory serine protease MASP-3 increased by 26% from baseline to week 1 (p<0.001) and remained high at week 7.
  
  
  CONCLUSIONS
  Our findings indicated that M-ficolin, MASP-2, and MASP-3 may act in concert to reduce the activity of the lectin pathway, in patients with CD who respond to biological therapy.
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark. Electronic address: Thomas.Damgaard.Sandahl@ki.au.dk.
authors.forename: Thomas Damgaard
authors.initials: TD
authors.lastname: Sandahl
authors.affiliation: Department of Medicine, Randers Regional Hospital, Randers, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Kelsen
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Dige
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jens Frederik
authors.initials: JF
authors.lastname: Dahlerup
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Agnholt
authors.affiliation: Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Christian Lodberg
authors.initials: CL
authors.lastname: Hvas
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000187:drug effects*; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D000069285:Infliximab; D037102:Lectins / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult; D000097604:Ficolins
chemical_list: D000068879:Adalimumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003165:Complement System Proteins; D006023:Glycoproteins; D000069285:Infliximab; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D014409:Tumor Necrosis Factor-alpha; D000097604:Ficolins; C109662:FCN3 protein, human; C084067:MASP1 protein, human; C105296:MASP2 protein, human
keywords: Anti-TNF-α therapy; Crohn's disease; Ficolin; Mannan-binding lectin