Depressed activation of the lectin pathway of complement in hereditary angioedema

L. Varga, G. Széplaki, J. Laki, A. Kocsis, K. Kristóf, P. Gál, Z. Bajtay, J. Wieslander, M. R. Daha, P. Garred, H. O. Madsen, G. Füst, H. Farkas

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Abstract

The possibility of simultaneous measurement of the classical pathway (CP), mannan-binding lectin (MBL)-lectin pathway (LP) and alternative pathway (AP) of complement activation by the recently developed Wielisa method allowed us to investigate the in vivo significance of the C1-inhibitor (C1INH) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP activity was found in patients compared with controls (P = 0.0008) in homozygous carriers of the normal MBL genotype (A/A), but not in carriers of variant genotypes (A/O, O/O). Activity of CP correlated with LP in patients (Spearman's r = 0.64; P <0.0001), but no significant correlation was found in the control group and no correlation with AP was observed. In contrast, the activity of CP and AP correlated (Spearman's r = 0.47; P <0.0001) in healthy controls, but there was no significant correlation in the HAE patients. We conclude that the activation of LP might also occur in subjects with C1INH deficiency, which is reflected by the low MASP-2 and C4 levels.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalClinical and Experimental Immunology
Volume153
Issue number1
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Mannose-Binding Lectin Complement Pathway
Hereditary Angioedemas
Mannose-Binding Lectin
Lectins
Mannose-Binding Protein-Associated Serine Proteases
Genotype
Alternative Complement Pathway
Complement Activation
Polymerase Chain Reaction
Control Groups
Serum

Keywords

  • Complement
  • ELISA
  • Immunodeficiency primary

ASJC Scopus subject areas

  • Immunology

Cite this

Depressed activation of the lectin pathway of complement in hereditary angioedema. / Varga, L.; Széplaki, G.; Laki, J.; Kocsis, A.; Kristóf, K.; Gál, P.; Bajtay, Z.; Wieslander, J.; Daha, M. R.; Garred, P.; Madsen, H. O.; Füst, G.; Farkas, H.

In: Clinical and Experimental Immunology, Vol. 153, No. 1, 07.2008, p. 68-74.

Research output: Contribution to journalArticle

Varga, L. ; Széplaki, G. ; Laki, J. ; Kocsis, A. ; Kristóf, K. ; Gál, P. ; Bajtay, Z. ; Wieslander, J. ; Daha, M. R. ; Garred, P. ; Madsen, H. O. ; Füst, G. ; Farkas, H. / Depressed activation of the lectin pathway of complement in hereditary angioedema. In: Clinical and Experimental Immunology. 2008 ; Vol. 153, No. 1. pp. 68-74.
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AU - Kristóf, K.

AU - Gál, P.

AU - Bajtay, Z.

AU - Wieslander, J.

AU - Daha, M. R.

AU - Garred, P.

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