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Dynamics of the immune response against extracellular products of group A streptococci during infection.
Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Biomedical Laboratory Science.
Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Biomedical Laboratory Science.
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2007 (English)In: Clinical and Laboratory Immunology, ISSN 1556-6811, Vol. 14, no 1, 44-51 p.Article in journal (Refereed) Published
Abstract [en]

The immune response against the infecting group A streptococcus (GAS) extracellular products (EP) was determined in acute- and convalescent-phase sera from 75 patients with different clinical manifestations of GAS infection. All EP elicited a high proliferative response in human peripheral blood mononuclear cells. In patients with bacteremia, low neutralization in acute-phase sera was associated with development of streptococcal toxic shock syndrome. Lack of neutralization in acute-phase sera was more common in patients infected with the T1emm1 serotype. The majority of patients did not develop the ability to neutralize the mitogenic activity of their infecting isolate despite a significant increase in enzyme-linked immunosorbent assay titer in early convalescent-phase sera. In patients with the ability to neutralize GAS EP, the immune response remained high over at least 3 years. In contrast, the neutralization capacity conferred by intravenous immunoglobulin and/or plasma treatment disappeared within 3 months.

Place, publisher, year, edition, pages
2007. Vol. 14, no 1, 44-51 p.
URN: urn:nbn:se:umu:diva-21777DOI: 10.1128/CVI.00271-06PubMedID: 17093101OAI: diva2:211876
Available from: 2009-04-20 Created: 2009-04-20 Last updated: 2011-09-16
In thesis
1. Superantigens in group A streptococcus: gene diversity and humoral immune response
Open this publication in new window or tab >>Superantigens in group A streptococcus: gene diversity and humoral immune response
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Group A streptococcus (GAS) is a strictly human pathogen that causes infections ranging from asymptomatic carriage to the highly lethal streptococcal toxic shock syndrome (STSS). GAS are classified according to the sequence of the variable 5’ end of the emm-gene that encodes the surface associated M-protein. In the late 1980s, outbreaks of GAS infections with high rates of STSS were reported in several parts of the world, including Sweden. Superantigens (SAgs), a group of exotoxins, have been described as key mediators of STSS due to their capacity to polyclonally activate T-cells and induce a massive release of inflammatory cytokines. Previous reports have revealed that sera from STSS patients have lower capacity to neutralize this SAg-mediated immune stimulation and a higher prevalence of GAS isolates with specific emm-genotypes during disease outbreaks. The aims of this thesis were to analyse the protective antibody response mounted by the host against SAgs produced by the infecting GAS isolate and to characterise the isolates emm-genotypes and SAg gene profiles. The clinical material examined was collected from patients with STSS, sepsis, erysipelas, or tonsillitis in Sweden between 1986 and 2001. Both acute- and convalescence-phase sera were analyzed, along with the infecting GAS isolates. The 92 clinical GAS isolates examined were found to exhibit a high degree of genetic diversity in terms of the number and identity of their SAg genes. Isolates with a given emm-genotype could be divided into subgroups on the basis of their SAg gene profiles. Ten different SAg gene profiles were identified in the 45 emm1 isolates examined; one of these ten was highly persistent, being observed in 22 isolates collected over 14 years. Two of the 11 known SAg genes in GAS, smeZ-1 and speA, were more prevalent in the emm1 associated profiles than in the SAg gene profiles of isolates with other emm-genotypes. Patients infected by GAS with the emm1-genotype were less likely to produce acute-phase sera that could effectively neutralize the T-cell mitogenicity induced by the infecting isolate’s extracellular products (EP). Sepsis patients whose sera exhibited this lack of neutralizing ability were more prone to developing STSS. Most patients whose acute-phase sera did not effectively neutralize the EP from the infecting isolate lacked protective antibodies in their convalescent-phase sera despite having elevated ELISA titers. The results reported herein show that combining SAg gene profiling with emm-genotyping may be useful for tracking the spread of GAS clones in the community. It was also shown that a lack of neutralizing activity in convalescence-phase sera might be due to an inability of those patients to mount a protective immune response against SAgs produced by the infecting GAS isolate.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2011. 60 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1432
Group A streptococcus, Streptococcus pyogenes, superantigen (SAg), SAg-gene profile, M-protein, emm-genotype
National Category
Microbiology in the medical area Biomedical Laboratory Science/Technology
Research subject
biomedicinsk laboratorievetenskap
urn:nbn:se:umu:diva-46454 (URN)978-91-7459-239-9 (ISBN)
Public defence
2011-10-07, E04, byggnad 6A, Norrlands Universitets Sjukhus, Umeå, 09:00 (English)
Available from: 2011-09-16 Created: 2011-09-02 Last updated: 2011-09-16Bibliographically approved

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