{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:08:28Z","timestamp":1790518108426,"version":"4.1.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Streptococcus pyogenes is an exclusively human pathogen that can provoke mild skin and throat infections but can also cause fatal septicemia. This gram-positive bacterium has developed several strategies to evade the human immune system, enabling S. pyogenes to survive in the host. These strategies include recruiting several human plasma proteins, such as the complement inhibitor, C4b-binding protein (C4BP), and human (hu)-IgG through its Fc region to the bacterial surface to evade immune recognition. We identified a novel virulence mechanism whereby IgG-enhanced binding of C4BP to five of 12 tested S. pyogenes strains expressed diverse M proteins that are important surface-expressed virulence factors. Importantly, all strains that bound C4BP in the absence of IgG bound more C4BP when IgG was present. Further studies with an M1 strain that additionally expressed protein H, also a member of the M protein family, revealed that binding of hu-IgG Fc to protein H increased the affinity of protein H for C4BP. Increased C4BP binding accentuated complement downregulation, resulting in diminished bacterial killing. Accordingly, mortality from S. pyogenes infection in hu-C4BP transgenic mice was increased when hu-IgG or its Fc portion alone was administered concomitantly. Electron microscopy analysis of human tissue samples with necrotizing fasciitis confirmed increased C4BP binding to S. pyogenes when IgG was present. Our findings provide evidence of a paradoxical function of hu-IgG bound through Fc to diverse S. pyogenes isolates that increases their virulence and may counteract the beneficial effects of IgG opsonization.<\/jats:p>","DOI":"10.4049\/jimmunol.1800090","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T16:31:19Z","timestamp":1523032279000},"page":"3495-3505","source":"Crossref","is-referenced-by-count":27,"title":["Human IgG Increases Virulence of <i>Streptococcus pyogenes<\/i> through Complement Evasion"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-9070","authenticated-orcid":false,"given":"David","family":"Ermert","sequence":"first","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University , 214 28 Malmo,","place":["Sweden"]},{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-0551","authenticated-orcid":false,"given":"Antonin","family":"Weckel","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University , 214 28 Malmo,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-0769","authenticated-orcid":false,"given":"Michal","family":"Magda","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University , 214 28 Malmo,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"M\u00f6rgelin","sequence":"additional","affiliation":[{"name":"Division of Infection Medicine, Department of Clinical Sciences, Lund University , 221 84 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-9954","authenticated-orcid":false,"given":"Jutamas","family":"Shaughnessy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bj\u00f6rck","sequence":"additional","affiliation":[{"name":"Division of Infection Medicine, Department of Clinical Sciences, Lund University , 221 84 Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-1734","authenticated-orcid":false,"given":"Anna M","family":"Blom","sequence":"additional","affiliation":[{"name":"Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University , 214 28 Malmo,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2025030610150280300_r1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","article-title":"The global burden of group A streptococcal diseases","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"2025030610150280300_r2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/CMR.13.3.470","article-title":"Pathogenesis of group A streptococcal infections","volume":"13","author":"Cunningham","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"2025030610150280300_r3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1056\/NEJM199601253340407","article-title":"Streptococcal infections of skin and soft tissues","volume":"334","author":"Bisno","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2025030610150280300_r4","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1126\/science.8209244","article-title":"Flesh-eating bacteria: not new, but still worrisome","volume":"264","author":"Nowak","year":"1994","journal-title":"Science"},{"key":"2025030610150280300_r5","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1073\/pnas.85.5.1657","article-title":"Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H","volume":"85","author":"Horstmann","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030610150280300_r6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1365-2958.1994.tb01003.x","article-title":"Protein H--a surface protein of Streptococcus pyogenes with separate binding sites for IgG and albumin","volume":"12","author":"Frick","year":"1994","journal-title":"Mol. Microbiol."},{"key":"2025030610150280300_r7","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1002\/j.1460-2075.1995.tb07156.x","article-title":"Protein H--a bacterial surface protein with affinity for both immunoglobulin and fibronectin type III domains","volume":"14","author":"Frick","year":"1995","journal-title":"EMBO J."},{"key":"2025030610150280300_r8","doi-asserted-by":"crossref","first-page":"32172","DOI":"10.1074\/jbc.M113.502955","article-title":"Binding of complement inhibitor C4b-binding protein to a highly virulent Streptococcus pyogenes M1 strain is mediated by protein H and enhances adhesion to and invasion of endothelial cells","volume":"288","author":"Ermert","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2025030610150280300_r9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.4049\/jimmunol.154.1.375","article-title":"Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system","volume":"154","author":"Thern","year":"1995","journal-title":"J. Immunol."},{"key":"2025030610150280300_r10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1365-2958.2005.04527.x","article-title":"Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway","volume":"56","author":"Carlsson","year":"2005","journal-title":"Mol. Microbiol."},{"key":"2025030610150280300_r11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000353754","article-title":"Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing","volume":"6","author":"Ly","year":"2014","journal-title":"J. Innate Immun."},{"key":"2025030610150280300_r12","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.4049\/jimmunol.1700426","article-title":"Factor H-IgG chimeric proteins as a therapeutic approach against the gram-positive bacterial pathogen Streptococcus pyogenes","volume":"199","author":"Blom","year":"2017","journal-title":"J. Immunol."},{"key":"2025030610150280300_r13","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.chom.2015.09.004","article-title":"Group A streptococcal M1 protein sequesters cathelicidin to evade innate immune killing","volume":"18","author":"LaRock","year":"2015","journal-title":"Cell Host Microbe"},{"key":"2025030610150280300_r14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/CMR.00101-13","article-title":"Disease manifestations and pathogenic mechanisms of group A Streptococcus","volume":"27","author":"Walker","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"2025030610150280300_r15","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.chom.2013.11.003","article-title":"The globally disseminated M1T1 clone of group A Streptococcus evades autophagy for intracellular replication","volume":"14","author":"Barnett","year":"2013","journal-title":"Cell Host Microbe"},{"key":"2025030610150280300_r16","doi-asserted-by":"crossref","first-page":"15854","DOI":"10.1074\/jbc.M113.469106","article-title":"Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors","volume":"288","author":"Honda-Ogawa","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2025030610150280300_r17","doi-asserted-by":"crossref","first-page":"e1002736","DOI":"10.1371\/journal.ppat.1002736","article-title":"DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition","volume":"8","author":"Uchiyama","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025030610150280300_r18","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement. First of two parts","volume":"344","author":"Walport","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"2025030610150280300_r19","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.molimm.2013.05.222","article-title":"Human complement control and complement evasion by pathogenic microbes--tipping the balance","volume":"56","author":"Zipfel","year":"2013","journal-title":"Mol. Immunol."},{"key":"2025030610150280300_r20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.imlet.2015.11.014","article-title":"C4b-binding protein: the good, the bad and the deadly. Novel functions of an old friend","volume":"169","author":"Ermert","year":"2016","journal-title":"Immunol. Lett."},{"key":"2025030610150280300_r21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/0161-5890(90)90071-7","article-title":"Protein H--a novel IgG binding bacterial protein","volume":"27","author":"Akesson","year":"1990","journal-title":"Mol. Immunol."},{"key":"2025030610150280300_r22","volume-title":"Streptococcus Pyogenes: Basic Biology to Clinical Manifestations.","author":"Fischetti","year":"2016"},{"key":"2025030610150280300_r23","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1093\/infdis\/jiu260","article-title":"A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development","volume":"210","author":"Sanderson-Smith","year":"2014","journal-title":"J. Infect. Dis."},{"key":"2025030610150280300_r24","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1473-3099(09)70178-1","article-title":"Global emm type distribution of group A streptococci: systematic review and implications for vaccine development","volume":"9","author":"Steer","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"2025030610150280300_r25","doi-asserted-by":"crossref","first-page":"20774","DOI":"10.1074\/jbc.272.33.20774","article-title":"Streptococcal protein H forms soluble complement-activating complexes with IgG, but inhibits complement activation by IgG-coated targets","volume":"272","author":"Berge","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2025030610150280300_r26","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1128\/IAI.67.4.1708-1714.1999","article-title":"Protein H, an antiphagocytic surface protein in Streptococcus pyogenes","volume":"67","author":"Kihlberg","year":"1999","journal-title":"Infect. Immun."},{"key":"2025030610150280300_r27","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.4049\/jimmunol.148.10.3238","article-title":"Protein Arp and protein H from group A streptococci. Ig binding and dimerization are regulated by temperature","volume":"148","author":"Akerstr\u00f6m","year":"1992","journal-title":"J. Immunol."},{"key":"2025030610150280300_r28","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1046\/j.1365-2958.2000.02084.x","article-title":"Virulent aggregates of Streptococcus pyogenes are generated by homophilic protein-protein interactions","volume":"37","author":"Frick","year":"2000","journal-title":"Mol. Microbiol."},{"key":"2025030610150280300_r29","doi-asserted-by":"crossref","first-page":"e1005043","DOI":"10.1371\/journal.ppat.1005043","article-title":"Virulence of group A streptococci is enhanced by human complement inhibitors","volume":"11","author":"Ermert","year":"2015","journal-title":"PLoS Pathog."},{"key":"2025030610150280300_r30","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1046\/j.1365-2958.2000.01942.x","article-title":"Generation of a mature streptococcal cysteine proteinase is dependent on cell wall-anchored M1 protein","volume":"36","author":"Collin","year":"2000","journal-title":"Mol. Microbiol."},{"key":"2025030610150280300_r31","first-page":"146","volume-title":"Dept. of Cell and Molecular Biology.","author":"Kihlberg","year":"1998"},{"key":"2025030610150280300_r32","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0882-4010(96)80003-9","article-title":"Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in mga","volume":"19","author":"Kihlberg","year":"1995","journal-title":"Microb. Pathog."},{"key":"2025030610150280300_r33","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1042\/bj3230469","article-title":"The amino-terminal module of the C4b-binding protein alpha-chain is crucial for C4b binding and factor I-cofactor function","volume":"323","author":"H\u00e4rdig","year":"1997","journal-title":"Biochem. J."},{"key":"2025030610150280300_r34","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/BF01120205","article-title":"Monoclonal antibodies against the complement control protein factor H (beta 1 H)","volume":"3","author":"Sim","year":"1983","journal-title":"Biosci. Rep."},{"key":"2025030610150280300_r35","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1042\/bj3000877","article-title":"M1 protein and protein H: IgGFc- and albumin-binding streptococcal surface proteins encoded by adjacent genes","volume":"300","author":"Akesson","year":"1994","journal-title":"Biochem. J."},{"key":"2025030610150280300_r36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0076-6879(87)45003-9","article-title":"Electron microscopy and other physical methods for the characterization of extracellular matrix components: laminin, fibronectin, collagen IV, collagen VI, and proteoglycans","volume":"145","author":"Engel","year":"1987","journal-title":"Methods Enzymol."},{"key":"2025030610150280300_r37","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1359\/jbmr.081112","article-title":"Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine\/human) RANKL","volume":"24","author":"Kostenuik","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"2025030610150280300_r38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-59745-204-5_21","article-title":"Fungal and bacterial killing by neutrophils","volume":"470","author":"Ermert","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"2025030610150280300_r39","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2025030610150280300_r40","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/bioinformatics\/btr595","article-title":"RAPSearch2: a fast and memory-efficient protein similarity search tool for next-generation sequencing data","volume":"28","author":"Zhao","year":"2012","journal-title":"Bioinformatics"},{"key":"2025030610150280300_r41","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1084\/jem.20120325","article-title":"Antibody orientation at bacterial surfaces is related to invasive infection","volume":"209","author":"Nordenfelt","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025030610150280300_r42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/BF01570188","article-title":"M-like, immunoglobulin-binding protein of Streptococcus pyogenes type M15","volume":"29","author":"Katerov","year":"1994","journal-title":"Curr. Microbiol."},{"key":"2025030610150280300_r43","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.4049\/jimmunol.150.6.2332","article-title":"Type M12 protein from Streptococcus pyogenes is a receptor for IgG3","volume":"150","author":"Retnoningrum","year":"1993","journal-title":"J. Immunol."},{"key":"2025030610150280300_r44","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.4049\/jimmunol.148.10.3174","article-title":"Identification of two type IIa IgG-binding proteins expressed by a single group A streptococcus","volume":"148","author":"Otten","year":"1992","journal-title":"J. Immunol."},{"key":"2025030610150280300_r45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/iai.25.1.1-10.1979","article-title":"Specific absorption of human serum albumin, immunoglobulin A, and immunoglobulin G with selected strains of group A and G streptococci","volume":"25","author":"Kronvall","year":"1979","journal-title":"Infect. Immun."},{"key":"2025030610150280300_r46","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1073\/pnas.86.12.4741","article-title":"Fc-receptor and M-protein genes of group A streptococci are products of gene duplication","volume":"86","author":"Heath","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030610150280300_r47","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/0161-5890(95)00022-7","article-title":"Characterization of a gene coding for a type IIo bacterial IgG-binding protein","volume":"32","author":"Boyle","year":"1995","journal-title":"Mol. Immunol."},{"key":"2025030610150280300_r48","doi-asserted-by":"crossref","first-page":"e78719","DOI":"10.1371\/journal.pone.0078719","article-title":"Non-immune binding of human IgG to M-related proteins confers resistance to phagocytosis of group A streptococci in blood","volume":"8","author":"Courtney","year":"2013","journal-title":"PLoS One"},{"key":"2025030610150280300_r49","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1371\/journal.ppat.0020047","article-title":"Extreme sequence divergence but conserved ligand-binding specificity in Streptococcus pyogenes M protein","volume":"2","author":"Persson","year":"2006","journal-title":"PLoS Pathog."},{"key":"2025030610150280300_r50","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1073\/pnas.071559398","article-title":"Complete genome sequence of an M1 strain of Streptococcus pyogenes","volume":"98","author":"Ferretti","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030610150280300_r51","doi-asserted-by":"crossref","first-page":"E1768","DOI":"10.1073\/pnas.1403138111","article-title":"Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences","volume":"111","author":"Nasser","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030610150280300_r52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1086\/432514","article-title":"Evolutionary origin and emergence of a highly successful clone of serotype M1 group a Streptococcus involved multiple horizontal gene transfer events","volume":"192","author":"Sumby","year":"2005","journal-title":"J. Infect. Dis."},{"key":"2025030610150280300_r53","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1128\/iai.61.8.3369-3374.1993","article-title":"Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome","volume":"61","author":"Talkington","year":"1993","journal-title":"Infect. Immun."},{"key":"2025030610150280300_r54","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/clinids\/21.5.1220","article-title":"Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone","volume":"21","author":"Carapetis","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"2025030610150280300_r55","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1128\/JCM.02155-08","article-title":"Clinical and microbiological characteristics of severe Streptococcus pyogenes disease in Europe","volume":"47","author":"Luca-Harari","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"2025030610150280300_r56","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1086\/599344","article-title":"Seven-year surveillance of North American pediatric group a streptococcal pharyngitis isolates","volume":"49","author":"Shulman","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"2025030610150280300_r57","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1017\/S095026880006739X","article-title":"Changes in the pattern of infection caused by Streptococcus pyogenes","volume":"100","author":"Gaworzewska","year":"1988","journal-title":"Epidemiol. Infect."},{"key":"2025030610150280300_r58","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1056\/NEJM199608223350803","article-title":"Invasive group A streptococcal infections in Ontario, Canada","volume":"335","author":"Davies","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2025030610150280300_r59","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3201\/eid1410.071660","article-title":"Rise and persistence of global M1T1 clone of Streptococcus pyogenes","volume":"14","author":"Aziz","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"2025030610150280300_r60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0378-1097(02)01184-9","article-title":"Regulation of protein H expression in M1 serotype isolates of Streptococcus pyogenes","volume":"219","author":"Smith","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"2025030610150280300_r61","doi-asserted-by":"crossref","first-page":"13688","DOI":"10.1021\/bi00041a051","article-title":"Structure and stability of protein H and the M1 protein from Streptococcus pyogenes. Implications for other surface proteins of gram-positive bacteria","volume":"34","author":"Nilson","year":"1995","journal-title":"Biochemistry"},{"key":"2025030610150280300_r62","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3109\/00365517409050824","article-title":"Interstitial fluid concentrations of albumin and immunoglobulin G in normal men","volume":"34","author":"Poulsen","year":"1974","journal-title":"Scand. J. Clin. Lab. Invest."},{"key":"2025030610150280300_r63","first-page":"101","article-title":"Serum immunoglobulin levels in healthy children and adults","volume":"4","author":"Stoop","year":"1969","journal-title":"Clin. Exp. Immunol."},{"key":"2025030610150280300_r64","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000332940","article-title":"Streptococcal IdeS and its impact on immune response and inflammation","volume":"4","author":"von Pawel-Rammingen","year":"2012","journal-title":"J. Innate Immun."},{"key":"2025030610150280300_r65","doi-asserted-by":"crossref","first-page":"7187","DOI":"10.1128\/IAI.69.11.7187-7189.2001","article-title":"Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins","volume":"69","author":"Collin","year":"2001","journal-title":"Infect. Immun."},{"key":"2025030610150280300_r66","volume-title":"Bacterial immunoglobulin binding proteins.","author":"Boyle","year":"1990"},{"key":"2025030610150280300_r67","doi-asserted-by":"crossref","first-page":"9862","DOI":"10.1074\/jbc.270.17.9862","article-title":"Streptococcal cysteine proteinase releases biologically active fragments of streptococcal surface proteins","volume":"270","author":"Berge","year":"1995","journal-title":"J. Biol. Chem."},{"key":"2025030610150280300_r68","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/j.1365-2958.2007.05841.x","article-title":"Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation","volume":"65","author":"Shannon","year":"2007","journal-title":"Mol. Microbiol."},{"key":"2025030610150280300_r69","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s101560100012","article-title":"Invasive streptococcal infections","volume":"7","author":"Stevens","year":"2001","journal-title":"J. Infect. Chemother."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/200\/10\/3495\/62231631\/ji1800090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/200\/10\/3495\/62231631\/ji1800090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T10:44:44Z","timestamp":1741257884000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/200\/10\/3495\/7966099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":69,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,5,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1800090","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,5]]},"published":{"date-parts":[[2018,5]]}}}