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J Crohns Colitis. 2014 Jun;8(6):521-8. doi: 10.1016/j.crohns.2013.11.007. Epub 2013 Nov 28.

The lectin pathway of the complement system is downregulated in Crohn's disease patients who respond to anti-TNF-α therapy.

Author information

1
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark. Electronic address: Thomas.Damgaard.Sandahl@ki.au.dk.
2
Department of Medicine, Randers Regional Hospital, Randers, Denmark.
3
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark.
4
Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Abstract

BACKGROUND AND AIMS:

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.

KEYWORDS:

Anti-TNF-α therapy; Crohn's disease; Ficolin; Mannan-binding lectin

PMID:
24291022
DOI:
10.1016/j.crohns.2013.11.007
[Indexed for MEDLINE]

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