A mutation in factor I that is strongly associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation

Sara C. Nilsson, Diana Karpman, Fariba Vaziri-Sani, Ann-Charlotte Kristoffersson, Remi Salomon, Francois Provot, Veronique Fremeaux-Bacchi, Leendert A. Trouw, Anna M. Blom

Forskningsoutput: TidskriftsbidragArtikel

Sammanfattning

Factor I (FI) is the major complement inhibitor that degrades C3b and C4b in the presence of cofactors C4b binding protein (C4BP), factor H (FH), membrane cofactor protein (MCP) or complement receptor 1 (CR1). Recently, mutations and polymorphisms in complement regulator molecules FH and MCP but also in FI have been associated with atypical hemolytic uremic syndrome (aHUS). HUS is a disorder characterized by hemolytic anemia, thrombocytopenia and acute renal failure. In this study we report three unrelated patients with an identical heterozygous mutation, G261D, in FI heavy chain who developed severe aHUS at different time points in their lives. Two patients also have polymorphisms in FH previously associated with risk of developing aHUS. Testing in particular one patient and control serum samples we did not observe major differences in complement hemolytic activity, FI plasma levels or the capability to degrade C4b or C3b. A recombinant protein was produced in order to analyze the functional consequences of the mutation. Mutant FI had a slightly different migration pattern during electrophoresis under reducing conditions. An alteration due to alternative splicing or glycosylation was ruled out, thus the altered migration may be due to proximity of the mutation to a cysteine residue. The recombinant mutant FI degraded C3b and C4b in a manner comparable to wild type protein. In conclusion, despite the strong association between the heterozygous mutation in FI and aHUS we did not observe any abnormalities in the function of FI regarding complement regulation.

OriginalspråkEngelska
Sidor (från-till)221-221
Antal sidor0
TidskriftMolecular Immunology
Volym44
Utgåva1-3
DOI
StatusPublicerad - 2007
Externt publiceradJa

Nationell ämneskategori

  • Cell- och molekylärbiologi (30108)

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