Elsevier

International Congress Series

Volume 1289, April 2006, Pages 121-124
International Congress Series

Superantigens in sepsis

https://doi.org/10.1016/j.ics.2005.11.014Get rights and content

Abstract

Sepsis is increasingly caused by Gram-positive bacteria. Super-antigens (SAg) are products of Gram-positive bacteria that are responsible for toxic shock syndrome, however their role in sepsis is generally unknown. We sought to determine a possible role for SAg in sepsis by looking for an altered Vβ profile on circulating T cells using monoclonal antibodies and flow cytometry. We studied 20 patients with septic shock admitted for intensive care and compared them to 11 non-septic adults. We found patients with sepsis had a different Vβ profile compared to controls. This suggests that SAg are pathogenic in some patients with sepsis.

Introduction

Sepsis remains a major killer in our society. In Australia mortality rates for severe sepsis are estimated to be between 30% and 40% despite advances in intensive care [1], [2]. Gram-positive organisms are now the predominant microorganisms identified as causative agents for sepsis, with mixed infections also becoming more common [3]. There is evidence to support synergy between conventional antigens and super-antigens (SAg) in relation to mortality in animal models of sepsis [4], [5]. SAg bypass the normal antigen presentation via MHC class II molecules and directly bind the lateral aspect of the T cell receptor (TCR) at the TCR Vβ region. Due to this method of binding, the signature feature of SAg activity is the expansion of T lymphocyte populations bearing the particular Vβ chain(s) that the SAg binds to [6]. We sought to determine a possible role for SAg in patients with severe sepsis by studying the Vβ profile of circulating T cells from a cohort of patients with severe sepsis.

Section snippets

Methods

Following institutional Ethics committee approval, 1.1 ml of whole blood was sampled serially from 20 patients with severe sepsis and 11 non-septic adult controls who were admitted to the intensive care unit (ICU) of The Royal Melbourne Hospital. The samples were stained with a panel of monoclonal antibodies directed against 24 Vβ segments (IO Test Beta Mark, PN IM3497 Immunotech, Mareille, France) in addition to CD4 (CD4 Leu -3a, PN 347324, Becton Dickinson Immunocytometry Systems, San Jose,

Results

Forty-three samples were taken from 20 patients aged from 17 to 83 years of age with severe sepsis and 11 samples from 11 non-septic controls. The 2 groups were of similar age and severity of illness but there were slightly more males in the sepsis group (Table 1). The mortality rate for the sepsis group was 25%.

Results showed the Vβ profile was significantly different between the two study groups (Table 2). There were a greater number of CD4+ and CD8+ Vβ segments that were abnormal in the

Conclusions

In a cohort of 20 patients with severe sepsis, the expression of 24 Vβ segments within the T-cell receptor on the surface of both CD4+ and CD8+ circulating lymphocytes was different compared to non-septic adults. The only reported bacterial ligand that can alter the Vβ profile is a SAg. These results suggest that in some patients with severe sepsis SAg may be pathogenic.

Acknowledgement

Christopher MacIsaac held an NHMRC Medical Postgraduate Research Scholarship for 2003 and 2004. Ms. Narelle Skinner and Ms. Vesna Markovska helped with editing of the manuscript.

References (8)

  • C. MacIsaac

    Rapid analysis of the Vbeta repertoire of CD4 and CD8 T lymphocytes in whole blood

    J. Immunol. Methods

    (2003)
  • S. Finfer

    Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units

    Intensive Care Med.

    (2004)
  • V. Sundararajan

    Epidemiology of sepsis in Victoria, Australia

    Crit. Care Med.

    (2005)
  • G.S. Martin

    The epidemiology of sepsis in the United States from 1979 through 2000

    N. Engl. J. Med.

    (2003)
There are more references available in the full text version of this article.

Cited by (2)

  • The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia

    2012, Microbes and Infection
    Citation Excerpt :

    A recent study showed that in addition to the conventional SAg that are encoded by mobile genetic elements, a novel, genome-encoded SAg plays an important role in the pathogenesis of necrotizing pneumonia caused by a methicillin-resistant, community-associated S. aureus strain, USA300 [16]. SAg also play an important role in the etiopathogenesis of sepsis and Kawasaki disease [17–20]. Given the significance of SAg in the pathogenesis of serious staphylococcal infections, it would be beneficial to neutralize SAg or antagonize their biological functions in vivo.

View full text