Neutralization of Multiple Staphylococcal Superantigens by a Single‐Chain Protein Consisting of Affinity‐Matured, Variable Domain Repeats

Yang, Xi; Buonpane, Rebecca A.; Moza, Beenu; Rahman, Ashrafur; Wang, Ningyan; Schlievert, Patrick M.; McCormick, John K.; Sundberg, Eric J.; Kranz, David M.

doi:10.1086/589776

Cited by 19 publications

(16 citation statements)

References 16 publications

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“…These studies are in their infancy, but it is expected that in the future such antibody cocktails may replace the need for the costly IVIG. Multiple studies have also been performed that show that engineered high-affinity (picomolar affinity) V␤-TCRs, which are uniquely specific to binding and inactivating superantigens, prevent fever and lethality due to concurrent treatment or pretreatment with superantigens or staphylococci and streptococci that produce them, as tested in rabbit models (44,231,252,316,317). These reagents have also been shown in multiple rabbit studies to be important in preventing lethality due to staphylococcal pneumonia (231) and in preventing vegetation formation in infective endocarditis (252).…”

Section: Passive Vaccination Against Superantigensmentioning

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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Section: Passive Vaccination Against Superantigensmentioning

confidence: 99%

Staphylococcal and Streptococcal Superantigen Exotoxins

et al. 2013

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“…Soluble forms of the engineered Vβ proteins produced in E. coli were shown to be effective inhibitors of SEB-mediated T-cell activation and completely neutralized the lethal activity of SEB in animal models. 113 More recently, the same group was able to express Vβ domains in tandem as a single-chain protein and neutralized the clinically important SAgs SEB and TSST-1 with a single agent demonstrating the feasibility of engineering a broader spectrum antagonist capable of neutralizing multiple toxins 114…”

Section: Novel Directions In Therapymentioning

confidence: 99%

Recent insights into atopic dermatitis and implications for management of infectious complications

Boguniewicz

Leung

2010

Journal of Allergy and Clinical Immunology

303

236

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Atopic dermatitis is a common, complex disease that frequently follows a chronic, relapsing course and impacts the quality of life of patients and families in a significant manner. New insights into the pathophysiology of AD point to an important role of structural abnormalities in the epidermis combined with immune dysregulation. Patients with AD have a unique predisposition to colonization or infection by a number of microbial organisms, most notably Staphylococcus aureus and herpes simpex virus. A multi-pronged approach directed at healing or protecting the skin barrier and addressing the immune dysregulation is necessary to improve the likelihood of successful outcomes. • Atopic dermatitis is a global health problem, strongly associated with asthma and allergic sensitization. Keywords• Compared to atopic dermatitis patients without FGN mutations, those patients with atopic dermatitis who have mutations in the FGN gene have disease that is earlier in onset, more severe and more persistent and more likely to be associated with asthma and allergic sensitization.• Most patients with atopic dermatitis are colonized by toxin-secreting S. aureus, even on normal-appearing skin.• Patients with atopic dermatitis with FLG mutations have been found to have an increased risk for eczema herpeticum.• Topical anti-inflammatory measures can reduce S. aureus colonization.What is still unknown? •The exact relationship between barrier dysfunction and immune dysregulation in atopic dermatitis.• What other skin barrier proteins besides filaggrin are essential for normal barrier function?• A full understanding of why patients with atopic dermatitis compared to other inflammatory dermatoses have more problems with microbial colonization and infection.• Specific biomarkers for atopic dermatitis and unique phenotypes.• Optimal individualized therapy.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public AccessAuthor Manuscript J Allergy Clin Immunol. Author manuscript; available in PMC 2011 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAtopic dermatitis (AD), a complex chronic relapsing inflammatory skin disorder continues to be an important disease worldwide. 1, 2 Lifetime prevalence in school aged children in the United States has been reported to be up to 17%.3 Similarly high prevalence rates have also been observed in a number of other countries.4 Most recently, data on eczema symptoms from over a million children in 97 countries showed that AD is a major problem in developing, as well as developed countries.5 Atopy remains an important as...

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“…Another action of SAgs is to directly block TCR interaction with the presented peptide, keeping the TCR and MHC II dimers physically separated where SAgs wedge between the two receptors (Group II), allowing only minimal contact (TCR α-chain and MHC II β-chain), physically block peptide interaction (Class 1), or bind to cause a sharp angle in between TCR and MHC II/peptide interface (class V) [57]. Current studies on SAgs involve development of structural mimics to neutralize pathology in animal models [61] and to determine the specificity of immune stimulation by SAgs of clinical bacterial isolates [62]. …”

Section: Superantigensmentioning

confidence: 99%

Toxins from bacteria

Henkel

Baldwin

Barbieri

2010

Experientia Supplementum

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Bacterial toxins damage the host at the site of bacterial infection or distanced from the site of infections. Bacterial toxins can be single proteins or organized as oligomeric protein complexes and are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity; ADP-ribosylation of host proteins is the earliest post-translational modification determine to be performed by bacterial toxin, and now include glucosylation and proteolysis among other s. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the section mechanism that delivers the toxin out of the bacterium, termed type I–VII. This review will overview the major families of bacterial toxins and will also describe the specific structure-function properties of the botulinum neurotoxins.

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Neutralization of Multiple Staphylococcal Superantigens by a Single‐Chain Protein Consisting of Affinity‐Matured, Variable Domain Repeats

Cited by 19 publications

References 16 publications

Staphylococcal and Streptococcal Superantigen Exotoxins

Staphylococcal and Streptococcal Superantigen Exotoxins

Recent insights into atopic dermatitis and implications for management of infectious complications

Toxins from bacteria

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