Genetic, molecular and functional analyses of complement factor I deficiency.

Nilsson, Sara (author): Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups

Trouw, Leendert (author): Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups

Renault, Nicolas (author)

Miteva, Maria A (author)

Genel, Ferah (author)

Zelazko, Marta (author)

Marquart, Hanne (author)

Muller, Klaus (author)

Sjöholm, Anders (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Truedsson, Lennart (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Villoutreix, Bruno O (author)

Blom, Anna M (author)

(creator_code:org_t)

2008-12-09
2009
English.
In: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 39:1, s. 310-323

Related links:: http://www.ncbi.nlm....; show more...; http://dx.doi.org/10...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patients with no detectable serum FI and also close family members revealed homozygous or compound heterozygous mutations in several domains of FI. These mutations were introduced into recombinant FI and the resulting proteins were purified for functional studies, while transient transfection was used to analyze expression and secretion. The G170V mutation resulted in a protein that was not expressed, whereas the mutations Q232K, C237Y, S250L, I339M and H400L affected secretion. Furthermore, the C237Y and the S250L mutants did not degrade C4b and C3b as efficiently as the WT. The truncated Q336x mutant could be expressed, in vitro, but was not functional because it lacks the serine protease domain. Furthermore, this truncated FI was not detected in serum of the patient. Structural investigations using molecular modeling were performed to predict the potential impact the mutations have on FI structure. This is the first study that investigates, at the functional level, the consequences of molecular defects identified in patients with full FI deficiency.

By the author/editor: Nilsson, Sara; Trouw, Leendert; Renault, Nicolas; Miteva, Maria A; Genel, Ferah; Zelazko, Marta; show more...; Marquart, Hanne; Muller, Klaus; Sjöholm, Anders; Truedsson, Lenna ...; Villoutreix, Bru ...; Blom, Anna M; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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