title: Impaired opsonization with complement and phagocytosis of Streptococcus pyogenes in sera from subjects with inherited C2 deficiency.
abstract: Although subjects with inherited defects of the classical complement pathway component C2 are at increased risk of infection, there are few experimental data available on which bacterial pathogens they might be susceptible to. In order to investigate whether patients with inherited C2 deficiency may have increased susceptibility to Streptococcus pyogenes infection we have analysed opsonization with C3b/iC3b and phagocytosis of three different strains of S. pyogenes in serum from 8 C2(-/-) subjects using flow cytometry assays. Sera from patients with C2 deficiency had a markedly reduced ability to opsonise S. pyogenes with C3b/iC3b. In addition, phagocytosis of all three S. pyogenes strains was impaired in sera from C2(-/-) subjects. Both the reduced opsonisation with C3b/iC3b and phagocytosis in C2(-/-) sera were markedly improved by addition of exogenous C2 protein. Neutrophil dependent killing was also reduced, confirming the functional importance of C2 deficiency for immunity to S. pyogenes. Impaired opsonisation with C3b/iC3b and phagocytosis was not related to reduced recognition of the bacteria by antibody. These data suggest that patients with C2 deficiency are at increased risk of S. pyogenes infections.
authors.affiliation: Centre for Respiratory Research, Royal Free and University College Medical School, Rayne Institute, London, United Kingdom. jyuste@cib.csic.es
authors.forename: Jose
authors.initials: J
authors.lastname: Yuste
authors.forename: Ashwin
authors.initials: A
authors.lastname: Sen
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Catherine
authors.initials: C
authors.lastname: Hyams
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cohen
authors.forename: Emilie
authors.initials: E
authors.lastname: Camberlein
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003175:Complement C2 / Q000172:deficiency*; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D050296:Microbial Viability; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding; D044967:Serum / Q000276:immunology* / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D055815:Young Adult
chemical_list: D003175:Complement C2; D003179:Complement C3b