Severe atopic dermatitis is associated with sensitization to staphylococcal enterotoxin B (SEB)

BACKGROUND: Staphylococcus aureus has been identified as a possible trigger factor in atopic dermatitis (AD). Some 30-60% of S. aureus strains isolated from patients with AD are able to produce exotoxins with superantigenic properties, mostly staphylococcal enterotoxins A, B, C, and D (SEA-D) and toxic shock syndrome toxin-1 (TSST-1). Recently, it was demonstrated that the presence of IgE antibodies to SEA and SEB is correlated with the severity of skin lesions in children with AD. To determine the relevance of staphylococcal enterotoxins in adult patients with AD, we investigated the relationship between the severity of skin lesions and sensitization to SEA and SEB. METHODS: Clinical severity was determined by the SCORAD index. Circulating IgE antibodies to SEA and SEB, serum eosinophil cationic protein (ECP) levels, and urine eosinophil protein X (EPX) levels were measured. RESULTS: The skin condition was significantly worse in patients sensitized to SEB than in unsensitized patients. Serum ECP and urine EPX levels were found to be significantly higher in SEB-sensitized patients, confirming the higher degree of cutaneous inflammation. CONCLUSIONS: Our results demonstrate a relationship between severity of skin lesions and sensitization to SEB in adult patients with AD, but a relationship between disease activity and sensitization to SEA could not be shown.     

Possible influences of Staphylococcus aureus on atopic dermatitis — the colonizing features and the effects of staphylococcal enterotoxins

BACKGROUND: Heavy colonization of atopic dermatitis (AD) with Staphylococcus aureus is well documented. This phenomenon suggests that S. aureus in AD lesions influences the disease processes of AD. OBJECTIVE: We describe the importance of the presence of S. aureus and staphylococcal enterotoxins A and B (SEA, SEB) in AD lesions. METHODS: We investigated the colonizing features of S. aureus in AD lesions using electron microscopy, the distribution of SEB in the eczematous skin of AD using immunofluorescence, the effects of SEA and SEB on normal human epidermal keratinocytes in organ culture, and the presence of specific IgE antibodies to SEA and/or SEB in serum of AD patients by enzyme immunoassay. RESULTS: S. aureus in AD lesions colonized on and in the horny layers of the eczematous skin. SEB produced by S. aureus was distributed mainly on the dermal-infiltrated cells, especially on eosinophils. SEA and SEB stimulated expression of ICAM-1 and HLA-DR in normal human keratinocytes. More than half of the AD patients in the present study had specific IgE antibodies to SEA and/or SEB in their serum. CONCLUSION: S. aureus and SEs have important roles in the exacerbation and prolongation of AD.     

Increased levels of serum-specific immunoglobulin e to staphylococcal enterotoxin a and B in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The association between staphylococcal enterotoxins and atopic dermatitis (AD) is well characterized. We aim to evaluate the association between sensitization to staphylococcal enterotoxin A (SEA) and/or B (SEB) and the development of allergic airway disease. METHODS: Two hundred and seventy-four patients were grouped into allergic rhinitis (AR) and/or bronchial asthma (BA) only, AD only and AR/BA+AD. The AR/BA only group was further divided into AR only, AR and airway hyperresponsiveness (AR+AHR) and BA. The allergen-specific and total immunoglobulin E (IgE) antibodies were determined by the CAP system. The associations of sensitization to SEA/SEB with allergic airway disease were analyzed by logistic regression analysis. RESULTS: The overall rate of sensitization to SEA/SEB was 25.7%, whereas the rate of the AD only group (45.5%) was significantly higher than that of the AR/BA only group (24.5%, chi2=8.1). After sensitization to SEA/SEB, the geometric mean total IgE levels were significantly elevated in patients with AR+AHR and BA, but not in those with AR only. BA patients had higher geometric mean values of SEA- and SEB-specific IgE than AR only and AR+AHR patients. Logistic regression revealed that AR/BA only was more associated with sensitization to SEA/SEB (odds ratio 6.57) than AD only and AR/BA+AD (odds ratio 2.44 and 1.72). CONCLUSIONS: Atopic status after sensitization to SEA/SEB was more closely associated with BA than with other airway allergy, implying that SEA/SEB may play a role in exacerbating airway allergy and increasing the risk of allergic airway disease. Our study suggests that staphylococcal enterotoxins play a prominent role in the pathogenesis of allergic airway disease as well as AD.     

Prevalence of serum IgE antibodies to the Staphylococcus aureus enterotoxins (SAE, SEB, SEC, SED, TSST-1) in patients with persistent allergic rhinitis

BACKGROUND: Enterotoxins produced by Staphylococcus aureus and their specific IgE antibodies were thought to be important in worsening atopic dermatitis. However, few studies have documented an association between S. aureus or its exotoxins and exacerbations of upper airway/nasal disease. In the current study, we determined the prevalence of serum-specific IgE towards staphylococcal enterotoxin A, B, C, D (SEA, SEB, SEC, SED) and toxic shock syndrome toxin 1 (TSST-1) in patients suffering from rhinitis and/or asthma due to allergy. Therefore, we examined whether SEA, SEB, SEC, SED and TSST-1 were important in worsening the clinical status of patients allergic to house dust mites by means of assessing serum eosinophil cationic protein (ECP), which is thought to be a reliable marker of asthma and rhinitis severity. METHODS: 198 patients with persistent allergic rhinitis and/or asthma due to house dust mites were evaluated. Specific IgE towards SEA, SEB, SEC, SED, TSST-1, timothy grass and birch pollen recombinant allergens, and other aeroallergen extracts from common allergen sources were evaluated by the Pharmacia CAP System. Serum ECP was assessed, too. RESULTS: The percentages of sensitization to staphylococcal enterotoxins of 198 house dust mite-allergic patients were as follows: TSST-1-specific IgE 24.7% (n=49), SEC-specific IgE 22.2% (n=44), SEB-specific IgE 15.1% (n=30), SEA-specific IgE 9.1% (n=18), and SED-specific IgE 5.5% (n=11). Out of 198 individuals allergic to house dust mites 136 patients suffering from persistent rhinitis were subdivided into two subgroups: 53 patients with serum-specific IgE to at least one staphylococcal enterotoxin and 83 patients without specific IgE towards staphylococcal enterotoxins. Patients sensitive to staphylococcal enterotoxins had higher serum ECP levels than patients lacking specific IgE to SEA, SEB, SEC, SED and TSST-1(geometric mean 24.3 vs. 16.6 microg/100 ml; p=0.029), as well as total IgE levels (geometric mean 564 vs. 161 kU/l, p=0.00063) and specific IgE to Dermatophagoides pteronyssinus (geometric mean 16.7 vs. 6.6 kU/l; p=0.0235) and Dermatophagoides farinae (geometric mean 18.6 vs. 7.8 kU/l; p=0.0246). CONCLUSION: A status of sensitization to staphylococcal enterotoxins seems to be a factor increasing serum ECP, which is thought to be a reliable marker of clinical severity of allergic disease. Therefore, the evaluation of SEA, SEB, SEC, SED and TSST-1-specific IgE antibodies may have additional significance for the prognosis of persistent allergic diseases of the upper airway.     

Presence of staphylococcal exfoliative toxin A in sera of patients with atopic dermatitis

BACKGROUND: It has been reported that the toxins that Staphylococcus aureus produces are associated with the exacerbation of atopic dermatitis (AD). It has been shown in many studies that staphylococcal enterotoxin (SE) A and SEB contribute to AD by humoral immunity through IgE production as a superantigen. On the other hand, little attention has been paid to the relationship between AD and exfoliative toxin x (ETx). OBJECTIVE: We investigated the toxins that are frequently detected from the skin of patients and how these toxins affect AD. METHODS: S. aureus, isolated from the skin of 100 patients with mild to severe AD, were examined for the producibility of toxins by polymerase chain reaction. Serum samples were obtained from 21 patients with mild and moderate AD. The levels of SEB, ETA, total IgE, specific IgE, and specific IgG in sera were measured by ELISA. RESULTS: SEB was most frequently detected from S. aureus on the skin of these patients as previously reported. And ETx, to which little attention has been paid so far, was frequently detected next to SEB. Furthermore, ETA was detected from the sera of almost all the AD patients. SEB was not detected at all. Although the level of ETA in the AD group was significantly higher than that of controls, ETA-specific IgE was not detected from their sera. High levels of ETA tended to be detected from infantile patients. Although there were no significant differences in the levels of ETA-IgG between AD and the controls, its prevalence was more than twice as high as the controls in AD. CONCLUSION: These results suggest that many AD patients were exposed to ETx. We conclude that ETx may contribute to exacerbation of AD, particularly in infants, by a mechanism that is not through specific IgE production, unlike SEB.     

Effects of TNCB sensitization in DS-Nh mice, serving as a model of atopic dermatitis, in comparison with NC/Nga mice

BACKGROUND: It has been predicted that a type-1 and type-2 helper T cell (Th1/Th2) imbalance exists in atopic dermatitis (AD). In DS-Nh mice, an AD mouse model, Staphylococcus aureus increases on the skin surface. OBJECTIVE: To investigate whether the Th1-dominant response has an influence on the development of AD, we induced chronic allergic hypersensitivity with 2,4,6-trinitrochlorobenzene (TNCB ) in two AD mouse models: NC/Nga mice and DS-Nh mice. Th1 and Th2 cytokine production of splenocytes was assessed under stimulation with staphylococcal enterotoxin B (SEB) which induces a Th1 response in DS-Nh mice with or without TNCB sensitization. METHODS: We examined clinical skin changes, transepidermal water loss (TEWL), the number of S. aureus on the skin and the serum IgE levels in these mice treated repeatedly with TNCB under conventional conditions (free of fur mites). The splenocytes of DS-Nh mice were cultured with SEB and the cytokine levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant skin changes were observed on the skin even where TNCB was not applied in both mice treated with TNCB. Increases in S. aureus on the skin and serum IgE levels were detected in DS-Nh mice, but not in NC/Nga mice. In DS-Nh mice, IFN-gamma and IL-13 production of splenocytes increased in the mice treated with TNCB. CONCLUSION: These results suggest that there might be a different mechanism of dermatitis induction between NC/Nga and DS-Nh mice. Th1 responses might play an important role in the development of dermatitis and increase in serum IgE levels in DS-Nh mice through an increase in IL-13 production.     

Association of specific IgE to staphylococcal superantigens with the phenotype of chronic urticaria

It has been well established that bacterial superantigens lead to the induction and aggravation of chronic inflammatory skin diseases. We investigated the clinical significance of serum specific immunoglobulin E (lgE) to the staphylococcal superantigens staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB), and toxic shock syndrome toxin (TSST)-1 in patients with chronic urticaria (CU), focusing on the differences in these prevalences between aspirin-intolerant CU (AICU) and aspirin-tolerant CU (ATCU) patients. Aspirin sensitivity was confirmed by oral aspirin provocation test. There were 66 patients AICU and 117 patients ATCU in the study. Serum IgE antibodies specific for SEA, SEB, and TSST-1 were measured by the ImmunoCAP test and the patients were compared with 93 normal controls (NC). The prevalences of serum specific IgE to staphylococcal superantigens were significantly higher in CU than in NC patients (IgE to SEA, 13.7% vs. 5.4%; IgE to SEB, 12.0% vs. 4.3%; IgE to TSST-1, 18.0% vs. 6.5%; p<0.05, respectively). The patients with specific IgE to SEA, SEB, and TSST-1 had higher serum total IgE levels and higher rates of atopy. Significant associations were noted between the prevalence of specific IgE to SEA and SEB and the HLA DQB1*0609 and DRB1*1302 alleles in the AICU group. We confirmed that a sub-population of patients with CU possesses serum IgE antibodies to SEA, SEB, and TSST- 1. Particularly, the IgE immune response to TSST-1 is associated with aspirin sensitivity in CU patients.     

Epicutaneous sensitization with superantigen induces allergic skin inflammation

BACKGROUND: Atopic dermatitis (AD) is characterized by skin infiltration with eosinophils and lymphocytes and expression of Th2 cytokines in acute skin lesions. The skin of patients with AD is frequently colonized with enterotoxin-secreting strains of Staphylococcus aureus. Staphylococcal enterotoxins have been implicated in the exacerbations of the inflammatory skin lesions in patients with AD. OBJECTIVE: We sought to determine whether epicutaneous (EC) sensitization of mice with staphylococcal enterotoxin B (SEB) results in allergic skin inflammation. METHODS: BALB/c mice were EC-sensitized with SEB. Their skin was examined for allergic inflammation and cytokine expression, and their splenocytes were examined for cytokine secretion in response to SEB. RESULTS: EC sensitization with SEB elicited a local, cutaneous, inflammatory response characterized by dermal infiltration with eosinophils and mononuclear cells and increased mRNA expression of the Th2 cytokine IL-4 but not of the Th1 cytokine IFN-gamma. EC-sensitized mice mounted a systemic Th2 response to SEB evidenced by elevated total and SEB-specific IgG1 and IgE. Although EC sensitization with SEB resulted in selective depletion of SEB-specific T-cell receptor Vbeta8+ cells from the spleen and sensitized skin, splenocytes from SEB-sensitized mice secreted relatively more IL-4 and less IFN-gamma than did saline-sensitized controls, consistent with Th2 skewing of the systemic immune response to the superantigen. CONCLUSION: These results suggest that EC exposure to superantigens skews the immune response toward Th2 cells, leading to allergic skin inflammation and increased IgE synthesis that are characteristic of AD.     

SEB-induced T cell apoptosis in atopic patients--correlation to clinical status and skin colonization by Staphylococcus aureus

INTRODUCTION: We asked whether in atopic dermatitis (AD) increased T cell apoptosis in staphylococcal enterotoxin B (SEB)-activated cultures of peripheral blood mononuclear cells (PBMCs) is characteristic of the exacerbation of the disease or connected with skin colonization by Staphylococcus aureus. MATERIAL/METHODS: The clinical status of the patients was evaluated using the SCORAD index. The number of bacteria colonizing patients' skin lesions was determined by the cfu method. Mononuclear cells isolated from peripheral blood were stimulated by SEB and the apoptosis of CD3+ cells in culture was determined by flow cytometry using the monoclonal antibody APO2.7. The cytokine production in the culture supernatants was determined by ELISA and Cytometric Bead Array kits. RESULTS: T cell apoptosis was increased, while the production of interferon (IFN)-gamma was reduced in cultures of PBMCs of AD patients during exacerbation. The proportion of CD3+ APO2.7+ cells positively correlated with the density of S. aureus recovered from skin lesions, but not with SCORAD index. By contrast, SCORAD index, but not S. aureus density, negatively correlated with IFN- gamma production. Furthermore it was found that the presence of S. aureus on uninvolved skin distinguishes a group of severe cases with high serum IgE level, increased T cell apoptosis, and reduced production of tumor necrosis factor alpha in SEB- -stimulated cultures. CONCLUSIONS: Among AD patients the increased activation-induced T cell apoptosis observed in SEB- -stimulated cultures is related to skin colonization by S. aureus. The presence of bacteria on uninvolved skin is a feature of a distinct group of AD patients.     

Staphylococcal enterotoxin induced IL‐5 stimulation as a cofactor in the pathogenesis of atopic disease: the hygiene hypothesis in reverse?

BACKGROUND: The incidence of Staphylococcus aureus (S. aureus) colonization on the skin of patients with atopic eczema/dermatitis syndrome (AEDS) is approximately 90% and a variety of evidence implicates epidermal staphylococcal infection as a pathogenic factor in atopic dermatitis. However, the mechanism(s) underlying the effects of this organism in the disease process are unclear. The cellular responses of AEDS suffers and asymptomatic atopic individuals to bacterial superantigens (SAg) were investigated in an attempt to elucidate the role of staphylococcal enterotoxin B (SEB) in atopic disease. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from normal nonatopic adults, asymptomatic atopic individuals, patients with active AEDS and patients with active allergic asthma. The cells were cultured for 24 or 96 h with house dust mite (HDM), SEB and phytohaemagluttinin (PHA), and the supernatants were assayed for cytokine levels. RESULTS: Staphylococcal enterotoxin B selectively stimulates the production of interleukin (IL)-5 in AEDS sufferers but not in asymptomatic atopics or nonatopics. Additionally, we observed comparable susceptibility to the IL-5-stimulatory effects of SEB in allergic asthmatics. CONCLUSIONS: Given the central role of IL-5-driven eosinophilia in progression from mild atopy to severe disease, these findings provide a plausible mechanism for the AEDS-promoting effects of staphylococcal SAg. Staphylococcal enterotoxin B may also have a similar role in atopic respiratory disease.     

Presence of IgE antibodies to bacterial superantigens and increased IL-13-producing T cells in myelitic patients with atopic diathesis

BACKGROUND: Superantigens are considered to exacerbate autoimmune inflammation through the expansion of autoreactive T cells; however, the immune response to bacterial superantigens has not been extensively studied in any type of myelitis. We recently reported the occurrence of a distinct type of myelitis in patients with atopic diathesis, which in a recent nationwide survey was reported to be widespread in Japan. The aim of this study was to investigate the presence of IgE antibodies to bacterial superantigens and the proportion of IL-13- or IL-5-producing CD4+ or CD8+ T cells in patients with myelitis and atopic diathesis. METHODS: Twenty-four myelitic patients with and 12 myelitic patients without hyperIgEemia, 28 patients with multiple sclerosis (MS) and 34 healthy controls were enrolled in this study. IgE antibodies to staphylococcal enterotoxins A (SEA) and B (SEB) in sera were measured using a liquid-phase enzyme immunoassay, and the intracellular production of IL-5 and IL-13 in peripheral blood CD4+ and CD8+ T cells was measured by flow cytometry. RESULTS: The myelitic patients with hyperIgEemia showed significantly higher positive rates of serum SEA/SEB-specific IgE antibodies (41.7 and 62.5%, respectively) than the healthy controls (5.9 and 8.8%), patients with MS (0 and 21.4%) and those with normoIgEemic myelitis (0 and 0%). Moreover, IL-13-producing CD4+ T cells and CD8+ T cells increased significantly in the myelitic patients with hyperIgEemia compared to the controls, while IL-5-producing CD4+ or CD8+ T cells did not. CONCLUSIONS: The IgE response to staphylococcal superantigens is heightened in myelitic patients with atopic diathesis, which might contribute to increases in IL-13-producing T cells and thus the development of myelitis.     

Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes

Staphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P < 0.01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vbeta-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vbeta families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vbeta families in circulating, CLA+, skin homing lymphocytes is of functional significance.     

Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters

BACKGROUND: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. OBJECTIVE: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. METHODS: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. RESULTS: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 10(10)/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. CONCLUSIONS: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization.     

Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis

BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking susceptibility to colonization with Staphylococcus aureus. Some strains of S aureus secrete exotoxins with T-cell superantigen activity (toxigenic strains), and abnormal T-cell functions are known to play a critical role in AD. OBJECTIVE: Our purpose was to examine the impact of superantigen production by skin-colonizing S aureus on disease severity. METHODS: In a cross-sectional study of 74 children with AD, the presence and density of toxigenic and nontoxigenic strains of S aureus was correlated with disease severity. In a subgroup of patients the T-cell receptor Vbeta repertoire of peripheral blood and lesional T cells was investigated and correlated with individual superantigen activity of skin-colonizing S aureus. RESULTS: Fifty-three percent of children with AD were colonized with toxigenic strains of S aureus producing staphylococcal enterotoxin C, staphylococcal enterotoxin A, toxic shock syndrome toxin-1, staphylococcal enterotoxin B, and staphylococcal enterotoxin D in decreasing frequency. Children colonized with toxigenic S aureus strains had higher disease severity compared with the nontoxigenic and S aureus-negative groups. Patients colonized with toxigenic S aureus exhibited shifts in the intradermal T-cell receptor Vbeta repertoire that correspond to the respective superantigen-responsive T-cell subsets. CONCLUSION: The data demonstrate that S aureus-released exotoxins can modulate disease severity and dermal T-cell infiltration.     

Increased serum nitrate levels in infants with atopic dermatitis

BACKGROUND: The pathogenesis of atopic dermatitis (AD) is still unknown. A recent study has shown that inducible nitric oxide synthase (iNOS) is expressed in the atopic skin lesion, suggesting the involvement of nitric oxide in the skin inflammation of AD. The purpose of the study was to examine serum nitrate (NO3) levels in relation to the disease severity in children with AD. METHODS: Serum nitrate levels were assessed in relation to the skin scores in 88 patients with atopic dermatitis (AD) (aged 0.4-8 years: mean+/-SD, 2.2+/-1.9, 41 boys and 47 girls) and 12 nonatopic children (aged 0.8-4 years: mean+/-SD, 1.8+/-0.9, seven boys and five girls). RESULTS: Serum nitrate levels of patients with AD were significantly increased as compared to nonatopic controls and were also correlated with the disease severity. The skin scores were significantly correlated with serum nitrate levels as well as peripheral eosinophil counts. CONCLUSION: Our results indicate that nitric oxide may be involved in the pathogenesis of vasodilation and erythema in AD skin.     

DS-Nh as an experimental model of atopic dermatitis induced by Staphylococcus aureus producing staphylococcal enterotoxin C

DS-Nh mice raised under conventional conditions spontaneously develop dermatitis similar to human atopic dermatitis (AD), which is associated with staphylococcal infection. In the present study, we show that Staphylococcus aureus producing staphylococcus exotoxin C (SEC) was recovered from the culture of the skin lesions of DS-Nh mice with AD-like dermatitis and that the serum levels of anti-SEC antibodies from these mice were elevated. We describe here how to promote experimental AD by epicutaneous injection with SEC-producing S. aureus to DS-Nh mice. In order to assess the role of SEC in the pathogenesis of AD, the mitogenic activity, TCRBV repertoire analysis and the production of IL-4 and IFN-gamma from spleen mononuclear cells (MNC) from DS-Nh stimulated by SEC were compared with those due to SEA, SEB and TSST. The weakest was the mitogenic activity of SEC, and higher IL-4 responses and lower IFN-gamma responses to SEC showed correlation with TCRBV8S2-positive T cells, which were selectively stimulated by SEC. We also demonstrate that SEC-producing S. aureus was able to survive in DS-Nh after intradermal injection. These results suggest a possible role for SEC in the pathogenesis of AD through host-S. aureus relationships.     

Application of Staphylococcal enterotoxin B on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism

BACKGROUND: The skin of patients with inflammatory skin diseases such as atopic dermatitis is frequently colonized with Staphylococcus aureus. Colonization with S aureus has been reported to exacerbate atopic dermatitis. Recent studies have demonstrated that S aureus isolated from the skin of patients with atopic dermatitis releases bacterial toxins that act as superantigens. We have previously applied the staphylococcal superantigen staphylococcal enterotoxin B (SEB) on intact human skin and found that the application led to induction of dermatitis. OBJECTIVE: The purpose of the study was to determine whether superantigen-induced dermatitis is primarily due to a T cell-superantigen-mediated reaction or represents nonspecific cytokine-driven inflammation. METHODS: We applied SEB, vehicle, and sodium lauryl sulfate on normal skin in healthy (n = 6) and atopic subjects (n = 6) and biopsy specimens were taken from all treated areas. The biopsy specimens from all subjects and peripheral blood from the atopic subjects were analyzed for the T-cell receptor (TCR) Vbeta repertoire with mAbs against TCR Vbeta 2, 3, 8.1, 12, 14, and 17. RESULTS: From all subjects, both healthy and patients with atopic dermatitis, skin biopsy specimens from SEB-treated areas demonstrated selective accumulation of T cells expressing SEB-reactive TCR Vbeta 12 and 17 (P <.05). This selective up-regulation was not found in the sodium lauryl sulfate-treated areas. CONCLUSION: Our data strongly support that superantigen-induced T-cell activation is involved in the dermatitis seen after experimental application of SEB on intact skin.     

Correlation between atopic diseases and tuberculin responses

BACKGROUND: In recent decades, the prevalence of atopic diseases has risen steadily in developed countries. The reasons for this increase are not clear. It has been hypothesized that a reduction in infections and immunization programs may contribute to the increase in the prevalence of atopic diseases. We investigated the relationship between tuberculin response and atopic disease. METHODS: A total of 538 (73.0%) atopic and 198 (27.0%) nonatopic children vaccinated with BCG were included in the study. All the children included in the study had neither been given BCG nor tuberculin skin-tested in the previous 6 months, nor did they have a condition known to cause anergy. All the children were given five tuberculin units PPD, and PPD indurations were recorded after 48 h. RESULTS: The PPD induration size was 6.8 +/- 5.6 mm (mean +/- SD) in atopic children and 7.4 +/- 5.9 mm in nonatopic children. The difference between the two groups was not significant (P > 0.05). The PPD induration sizes of children with asthma, rhinitis, and atopic dermatitis were found to be similar. The children with atopic dermatitis had lower PPD induration size, but this was not statistically significant (P> 0.05). The rates of negative (< 5 mm skin induration) and intermediate (5-9 mm) responses were 32.6% and 30.5% in atopic children and 30.2% and 32.4% in nonatopic children, respectively. Positive tuberculin responses (PPD > 10 mm) were recorded in 36.9% of atopic children and 37.4% of nonatopic children. Total serum IgE levels of atopic and nonatopic children were 623.35 and 46.78 IU/ml, respectively. There was no correlation between serum total IgE level and PPD induration size (r = - 0.0012, P = 0.737). CONCLUSIONS: We did not find any relationship between tuberculin response and atopy status later in life in BCG-immunized subjects. We need further studies to clarify the effect of BCG on the development of atopy.     

Food-specific immunoglobulin E among children with atopic dermatitis: a retrospective study.

This retrospective study included 133 children aged between 2 and 16 years with elevated serum food-specific immunoglobulin E (IgE), including 59 children clinically diagnosed with atopic dermatitis (AD) and 74 children clinically diagnosed with atopic disease without AD (asthma, allergic rhinitis, or both). Six common serum food-specific IgEs were detected by the Pharmacia ImmunoCAP test, including: egg white, milk, peanut, soybean, shrimp and egg yolk. Serum total IgE was also measured. The results showed that both AD and non-AD atopic children had the highest sensitization rate to shrimp. AD children had significantly higher serum total IgE and average number of positive food sensitization items than atopic children without AD. Three serum food-specific IgEs, including peanut, soybean and egg yolk, were significantly higher in children with AD than in those without AD. Furthermore, 3 pairs of food-specific IgEs were correlated with each other in AD children: egg white IgE correlated with peanut IgE, egg white IgE correlated with egg yolk IgE, and peanut IgE correlated with soybean IgE. In logistic regression analysis of the serum of 6 food allergen-specific IgEs in AD children, we found that elevated peanut- and egg yolk-specific IgE were risk factors of AD in elevated serum food-specific IgE children whose serum total IgE was less than 1000 kU/L but not in those with total IgE greater than 1000 kU/L.     

Linoleic acid metabolite levels and transepidermal water loss in children with atopic dermatitis.

BACKGROUND: It has been suggested that atopic dermatitis (AD) is associated with impaired delta-6 desaturase activity and the subsequent altered composition of n-6 essential fatty acids (EFAs). OBJECTIVE: To investigate whether n-6 EFA deficiency accounts for AD by affecting transepidermal water loss or the immune response. METHODS: Serum levels of n-6 EFAs were measured using gas chromatography-mass spectrometry in a well-defined group of 35 children with AD (IgE level >150 U/mL); 35 age-matched children with allergic rhinitis, asthma, or both (IgE level >150 U/mL); and 31 nonatopic controls (IgE level <100 U/mL). Skin barrier function was evaluated by measuring transepidermal water loss and severity of AD by computing the Scoring Atopic Dermatitis (SCORAD) index. RESULTS: Atopic children had higher levels of linoleic acid (LA) and lower levels of its metabolites. Furthermore, gamma-linolenic acid to LA and dihommo-gamma-linolenic acid to LA ratios were significantly reduced in atopic patients. Transepidermal water loss and the SCORAD index were negatively correlated with serum levels of LA metabolites. There was no correlation between the SCORAD index and IgE level (P = .51) or between n-6 EFA concentrations and IgE level (P > .10). CONCLUSIONS: Deficits in n-6 EFAs were correlated with the severity of AD by affecting skin barrier function and cutaneous inflammation. The link between impaired n-6 EFA metabolism and IgE level could not be defined.