The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency.

Abstract

BACKGROUND AND OBJECTIVE:

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in patients with HAE-C1-INH.

METHODS:

The serum concentrations of ficolin-2, ficolin-3, MBL, MASP-2, MASP-3, and MAP-1 were measured during symptom-free periods in 91 patients with HAE-C1-INH, and in 100 healthy controls using sandwich ELISAs.

RESULTS:

Compared with controls, the levels of ficolin-2 (p<0.0001) and MASP-2 (p=0.0238) were reduced, while the levels of MBL and MASP-3 were elevated (p=0.0028 and p<0.0001, respectively) in HAE-C1-INH patients. Ficolin-3 and MAP-1 levels did not differ significantly between the two groups. Ficolin-2 correlated with MASP-3 in patients (r=0.3443, p=0.0008), while these parameters showed an opposite relationship in controls (r=-0.4625, p<0.0001). In the patients, ficolin-3 correlated with MASP-2 (r=0.3698, p=0.001). Ficolin-2, -3, and MAP-1 correlated negatively with the annual requirement of plasma derived C1-INH concentrate (r=-0.2863, p=0.0059; r=-0.2654, p=0.0110 and r=-0.2501, p=0.0168, respectively). Ficolin-3 showed a negative correlation with the annual number of attacks (r=-0.2478, p=0.0179).

CONCLUSIONS:

We found significant differences between patients and controls in the levels of some of the molecules belonging to the lectin complement pathway. Low concentrations of particularly ficolin-2 and -3 were inversely correlated with the severity of HAE-C1-INH, while this was not observed for MBL. This suggests a previously unrecognized involvement of the ficolin-dependent lectin complement pathway in the pathophysiology of HAE-C1-INH.

• Authors: Dorottya Csuka, Lea Munthe-Fog, Mikkel-Ole Skjoedt, Andrea Kocsis, Zsuzsanna Zotter, Péter Gál, Lilian Varga, Henriette Farkas, George Füst, Peter Garred
• Journal: Molecular immunology (Mol Immunol) Vol. 54 Issue 3-4 Pg. 271-7 (Jul 2013) ISSN: 1872-9142 [Electronic] England
• PMID: 23318225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• Complement C1 Inhibitor Protein
• FCN3 protein, human
• Glycoproteins
• Lectins
• MOAP1 protein, human
• ficolin
• MASP1 protein, human
• MASP2 protein, human
• Mannose-Binding Protein-Associated Serine Proteases

Topics

• Adaptor Proteins, Signal Transducing (blood, metabolism)
• Adult
• Aged
• Apoptosis Regulatory Proteins (blood, metabolism)
• Case-Control Studies
• Complement C1 Inhibitor Protein (metabolism)
• Complement Pathway, Mannose-Binding Lectin
• Female
• Glycoproteins (blood, metabolism)
• Hereditary Angioedema Types I and II (blood, metabolism)
• Humans
• Lectins (blood, metabolism)
• Male
• Mannose-Binding Protein-Associated Serine Proteases (metabolism)
• Middle Aged
• Young Adult