title: Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
abstract: Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.
authors.affiliation: Department of Clinical Sciences, Division of Infection Medicine, Lund University, BMC, B14, Lund, Sweden. fredrik.kahn@med.lu.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Kahn
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Oonagh
authors.initials: O
authors.lastname: Shannon
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Anders I
authors.initials: AI
authors.lastname: Olin
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D007249:Inflammation / Q000209:etiology* / Q000276:immunology / Q000382:microbiology; D009504:Neutrophils / Q000382:microbiology; D013290:Streptococcal Infections / Q000473:pathology; D013297:Streptococcus pyogenes / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; C014689:streptococcal M protein; D005340:Fibrinogen
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