antibodies against a surface protein of streptococcus pyogenes promote a pathological inflammatory response酿脓链球菌表面蛋白的抗体促进病理炎症反应.pdfVIP

Antibodies against a Surface Protein of Streptococcus pyogenes Promote a Pathological Inflammatory Response 1 ¨ 1 1 2 1 Fredrik Kahn *, Matthias Morgelin , Oonagh Shannon , Anna Norrby-Teglund , Heiko Herwald , 1 ¨ 1 Anders I. Olin , Lars Bjorck 1 Department of Clinical Sciences, Division of Infection Medicine, Lund University, BMC, B14, Lund, Sweden, 2 Karolinska Institute, Center for Infection Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden 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. ¨ Citation: Kahn F, Morgelin M, Shannon O, Norrby-Teglund A, Herwald H, et al. (2008) Antibodies against a Surface Protein of St