Staphylococcal Toxic Shock Syndrome Erythroderma Is Associated with Superantigenicity and Hypersensitivity

John, Chandy C.; Niermann, Micah; Sharon, Bazak; Peterson, Marnie L.; Kranz, David M.; Schlievert, Patrick M.

doi:10.1086/648441

Cited by 22 publications

(13 citation statements)

References 11 publications

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“…Exposure to SAgs that are either preformed (as in intentional exposure following attacks with biological weapons containing SAgs) or produced in vivo after bacterial infection can cause potent immune activation. In certain conditions, this immune activation can be robust, leading to a severe systemic cytokine storm (eg, TSS, Kawasaki disease, and neonatal TSS-like exanthematous disease 4,10,11 ). While SIRS leads to MODS and death, in the absence of prompt intervention, 3 the immunopathogenesis of this process is poorly understood because of lack of a robust animal model.…”

Section: Discussionmentioning

confidence: 99%

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Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

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Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as D-galactosamine (D-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without D-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4 ؉ and CD8؉), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the D-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with

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Section: Discussionmentioning

confidence: 99%

“…033. tribute to the pathogenesis of the associated disease. [8][9][10] The severity of disease is probably determined by the quantitative and qualitative characteristics of the SAg. Toxic shock syndrome (TSS) is one of the most serious clinical syndromes caused by S. aureus and S. pyogenes and their SAgs.…”

mentioning

confidence: 99%

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

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“…Our approach has involved the use of soluble, high-affinity receptors that could neutralize the toxins in much the same way as the TNF-␣-neutralizing agent Enbrel, a soluble form of the TNF-␣ receptor, neutralizes its target (6). Our previous success in animal models using a soluble high-affinity V␤ domain against SEB (G5-8) suggested that this approach has potential (9,21). Here, we have generated high-affinity V␤ against SpeA and explored the possible uses of V␤ agents in neutralizing multiple SAgs, such that the same drug might be used against different infectious agents.…”

Section: Discussionmentioning

confidence: 99%

A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from BothStaphylococcus aureusandStreptococcus pyogenes

Wang

Mattis

Sundberg

et al. 2010

Clin Vaccine Immunol

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Staphylococcus aureus and Streptococcus pyogenes secrete exotoxins that act as superantigens, proteins that cause hyperimmune reactions by binding the variable domain of the T-cell receptor beta chain (V␤), leading to stimulation of a large fraction of the T-cell repertoire. To develop potential neutralizing agents, we engineered V␤ mutants with high affinity for the superantigens staphylococcal enterotoxin B (SEB), SEC3, and streptococcal pyrogenic exotoxin A (SpeA). Unexpectedly, the high-affinity V␤ mutants generated against SEB cross-reacted with SpeA to a greater extent than they did with SEC3, despite greater sequence similarity between SEB and SEC3. Likewise, the V␤ mutants generated against SpeA cross-reacted with SEB to a greater extent than with SEC3. The structural basis of the high affinity and cross-reactivity was examined by single-site mutational analyses. The cross-reactivity seems to involve only one or two toxin residues. Soluble forms of the cross-reactive V␤ regions neutralized both SEB and SpeA in vivo, suggesting structure-based strategies for generating high-affinity neutralizing agents that can cross-react with multiple exotoxins.

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“…It is now recognized that often one of the defining criteria is not present; this illness is considered probable staphylococcal TSS (99). The defining criterion most often missing is the scarlet fever-like rash that occurs in association with preexistent delayed hypersensitivity to staphylococcal superantigens (61,150). However, cases of probable TSS in which each defining criterion has been absent have been described.…”

Section: Staphylococcal Menstrual Tssmentioning

confidence: 99%

Staphylococcal and Streptococcal Superantigen Exotoxins

et al. 2013

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SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.

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Staphylococcal Toxic Shock Syndrome Erythroderma Is Associated with Superantigenicity and Hypersensitivity

Cited by 22 publications

References 11 publications

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

A Single, Engineered Protein Therapeutic Agent Neutralizes Exotoxins from BothStaphylococcus aureusandStreptococcus pyogenes

Staphylococcal and Streptococcal Superantigen Exotoxins

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