Superantigens in 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.
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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.
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The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
2012, Microbes and InfectionCitation 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.
egc Superantigens Impair Monocytes/Macrophages Inducing Cell Death and Inefficient Activation
2020, Frontiers in Immunology