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Ficolin-3 (Hakata antigen or H-ficolin) is a soluble pattern recognition molecule in the lectin complement pathway. We speculated whether common genetic variations in the
FCN3 gene contribute to deficiency of Ficolin-3.
The
FCN3 gene was sequenced in 237 healthy Danish Caucasians. The relevance of polymorphisms was assessed with antibodies against Ficolin-3 in a novel ELISA system and by production of recombinant Ficolin-3 variants. Ficolin-3 serum profiles were analyzed by SDS-PAGE and western blotting.
Ficolin-3 serum concentration varied 10-fold (median, 24
μg/ml; range, 3–54
μg/ml). Out of several polymorphisms one
FCN3
+
1637delC causing a reading frame shift and a distortion of the C-terminal end of the molecule with an allele frequency of 0.011 was particularly interesting. In individuals heterozygous for the
FCN3
+
1637delC deletion lowered Ficolin-3 concentration was observed (
P
=
0.025). SDS-PAGE and western blotting of serum revealed a weak band corresponding to the truncated molecule in addition to the normal Ficolin-3 pattern. Characterization of recombinant Ficolin-3 derived from
FCN3
+
1637delC showed that in the homozygous situation this allelic variant would lead to Ficolin-3 deficiency.
In conclusion an
FCN3
+
1637delC deletion variant disrupting the possibility for pattern recognition was detected. Characterization of recombinant variant Ficolin-3 shows that homozygosity for the
FCN3
+
1637delC deletion may lead to Ficolin-3 deficiency and may thus be the basis for a novel complement deficiency state.