Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP(R). Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis.
Antibodies ; Enterotoxins ; Genotype ; Haplotypes ; Humans ; Immunoglobulin E* ; Polymorphism, Single Nucleotide ; Prevalence ; Shock, Septic ; Superantigens* ; Tyrosine ; Urticaria*

No anstract available.
Animal ; Binding Sites ; Histocompatibility Antigens Class II/chemistry/immunology/*metabolism ; Human ; Superantigens/chemistry/immunology/*metabolism

BACKGROUND AND OBJECTIVES: Superantigens such as Staphylococcus aureus exotoxin (SE) have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (NP). The aim of this study was to determine the immunologic response of peripheral blood mononuclear cells (PBMCs) to staphylococcal exotoxin B (SEB) in patients with NP. METHODS: The interleukin (IL)-4, IL-5, and interferon-gamma(IFN-gamma) responses of PBMCs to nonspecific mitogens such as phylohemagglutin (PHA) and SEB were examined in 24 NP patients and 16 control subjects. The presence or absence of atopy and asthma was determined to evaluate the correlation of these conditions with the levels of cytokines. RESULTS: PBMCs from the NP patients were more likely to produce IL-4 and IL-5 in response to SEB than those from controls. There was no difference in the mitogen-induced cytokine responses between NP patients and controls. SEB-induced IL-5 and IL-4 levels were higher in patients with NP with asthma than in patients with NP without asthma. CONCLUSION: Patients with NP show an exaggerated Th2 cytokine response of PBMCs to SEB.
Asthma ; Exotoxins ; Humans ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Mitogens ; Staphylococcus ; Staphylococcus aureus ; Superantigens

Superantigens are potent immunostimulatory exotoxins well known to be produced by Staphylococcus aureus (S. aureus). These exotoxins have capacity to act as superantigens by binding with the variable beta(Vbeta) region of lymphocytes in chronic rhinosinusitis with nasal polyposis, bypassing normal antigen processing and directly stimulating a massive inflammatory response. Accumulated evidence is now convincing that S. aureus superantigens may play an important role in development of chronic rhinosinusitis with nasal polyposis which are thought to skew the cytokine response towards a Th2 phenotype inducing eosinophilia and the production of polycolonal IgE. This review summarizes the current evidence of characteristics and its role superantigens in pathophysiology of nasal polyposis.
Antigen Presentation ; Eosinophilia ; Exotoxins ; Immunoglobulin E ; Lymphocytes ; Nasal Polyps ; Phenotype ; Staphylococcus aureus ; Superantigens

Superantigens are potent immunostimulatory exotoxins well known to be produced by Staphylococcus aureus (S. aureus). These exotoxins have capacity to act as superantigens by binding with the variable beta(Vbeta) region of lymphocytes in chronic rhinosinusitis with nasal polyposis, bypassing normal antigen processing and directly stimulating a massive inflammatory response. Accumulated evidence is now convincing that S. aureus superantigens may play an important role in development of chronic rhinosinusitis with nasal polyposis which are thought to skew the cytokine response towards a Th2 phenotype inducing eosinophilia and the production of polycolonal IgE. This review summarizes the current evidence of characteristics and its role superantigens in pathophysiology of nasal polyposis.
Antigen Presentation ; Eosinophilia ; Exotoxins ; Immunoglobulin E ; Lymphocytes ; Nasal Polyps ; Phenotype ; Staphylococcus aureus ; Superantigens

Chronic rhinosinusitis (CRS) is a multifactorial and heterogeneous disease, and variousfactors, such as inflammation, infection, fungus, and superantigens, have been proposed to play crucial roles in its pathogenesis. Recently, the dominant mechanismof CRS pathogenesis has shiftedfrom microbial infection and environmental factors to host susceptibility. Host susceptibility relies not only on adaptive immunity, but also on innate immunity, and there has recently been much research into innate immunity. Innate immunity is an evolutionally conserved immune system that recognizes microbial signature molecules via pattern recognition receptors and is a primary defense system that elicits inflammatory and bactericidal responses. Dysfunction of the host response to pathogens is suggested to be involved in pathogenesis of CRS and an irrelevant response of the host's innate immunity could cause a failure toeradicate the pathogens, thereby contributing to CRS pathogeneses. Among these innate immune systems, toll-like receptors and epithelial barrier functions have been studied extensively, and new players, such as innate lymphoid cells,have beensurfacing. Betterunderstanding of innate immunity couldhelp to investigateand treat this complex disease. In this review, toll-like receptors, epithelial barrier functions, and innate lymphoid cells,among many subjects related to innate immunity,will be discussed in terms of pathogenesis.
Adaptive Immunity ; Fungi ; Immune System ; Immunity, Innate* ; Inflammation ; Receptors, Pattern Recognition ; Superantigens ; Toll-Like Receptors

Antigens, Bacterial ; Humans ; Inflammation ; Nasal Mucosa ; immunology ; Staphylococcus ; immunology ; Superantigens ; immunology

OBJECTIVE: To construct an eukaryotic expression vectors containing superantigen staphylococcal enterotoxin A (SEA) gene, and to identify its expression in laryngeal squamous carcinoma cells. METHOD: SEA full-length gene fragment was obtained from ATCC13565 genome of the staphylococcus, referencing standard strains producing SEA. Coding sequence of SEA was artificially synthetized. Than, SEA gene fragments was subcloned into eukaryotic expression vector pIRES-EGFP. The recombinant plasmid pSEA-IRES-EGFP was constructed and was transfected to laryngocarcinoma Hep-2 cells. Resistant clones were screened by G418. The expression of SEA in laryngocarcinoma cells was identified with ELISA and RT-PCR method. RESULT: The subclone of artificially synthetized SEA gene was subclone to eukaryotic expression vector pires-EGFP. Flanking sequence confirmed that SEA sequence was fully identical to the coding sequence of standard staphylococcus strains ATCC13565 in Genbank. After recombinant plasmid transfected to laryngocarcinoma cells, the resistant clones was obtained after screening for two weeks. The clones were selected. The specific gene fragment was obtained by RT-PCR amplification. ELISA assay confirmed that the content of SEA protein in supernatant fluid of cell culture had reached about Pg level. CONCLUSION The recombinant eukaryotic expression vector containing superantigen SEA gene is successfully constructed, and is capable of effective expression and continued secretion of SEA protein in laryngochrcinoma Hep-2 cells after recombinant plasmid transfected to laryngocarcinoma cells.
Cell Line, Tumor ; Enterotoxins ; genetics ; Gene Expression ; Genetic Vectors ; Humans ; Plasmids ; Superantigens ; genetics ; Transfection

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell

Interleukin 5 (IL-5) is a key cytokine involved in the induction of T-helper type 2 (Th2) responses in the asthmatic airway. We investigated IL-5 genetic polymorphisms associated with asthma phenotypes, including IgE responses to staphylococcal enterotoxins A and B (SEA and SEB, respectively), in asthmatics. Adult asthmatics (n=310) and normal controls (n=160) were enrolled in the present study. Serum total and specific IgE to SEA and SEB were measured. Two IL-5 polymorphisms, -746A>G and +4499T>G, were genotyped using the primer-extension method. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the two groups. Asthmatics carrying the AG/GG genotype at -746A>G had a significantly higher prevalence of serum specific IgE to SEA (P=0.008), higher total IgE levels (P=0.014), and lower PC20 methacholine levels (P=0.002) compared to those with the AA genotype. These findings suggest that the IL-5 promoter polymorphism at -746A>G enhances serum total and specific IgE responses to SEA, which may augment airway hyperresponsiveness in adult asthmatics.
Adult ; Asthma ; Enterotoxins ; Genotype ; Haplotypes ; Humans ; Immunoglobulin E ; Interleukin-5 ; Lifting ; Methacholine Chloride ; Phenotype ; Polymorphism, Genetic ; Prevalence ; Superantigens