Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes

Karita Haapasalo, Hanna Jarva, Tuula Siljander, Wezenet Tewodros, Jaana Vuopio-Varkila, T. Sakari Jokiranta

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.
Original languageEnglish
JournalMolecular Microbiology
Volume70
Issue number3
Pages (from-to)583-594
Number of pages12
ISSN0950-382X
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Bibliographical note

This article has an erratum:Doi 10.1111/j.1365-2958.2012.07991.x

Fields of Science

  • HEMOLYTIC-UREMIC SYNDROME
  • HEPARIN-BINDING DOMAIN
  • SHORT CONSENSUS REPEAT
  • GROUP-A STREPTOCOCCI
  • C-REACTIVE PROTEIN
  • RCA GENE-CLUSTER
  • MACULAR DEGENERATION
  • ALTERNATIVE PATHWAY
  • C3B/C4B RECEPTOR
  • SURFACE PROTEIN
  • 3111 Biomedicine

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