Association between specific IgE to staphylococcal enterotoxin B and the eosinophilic phenotype of asthma.

BACKGROUND/AIMS: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. METHODS: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/µL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). RESULTS: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/clinfree IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). CONCLUSION: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.

Phylogenetic distribution and expression of a penicillin-binding protein homologue, Ear and its significance in virulence of Staphylococcus aureus.

PURPOSE: Staphylococcus aureus is an opportunistic human pathogen that can cause serious infections in humans. A plethora of known and putative virulence factors are produced by staphylococci that collectively orchestrate pathogenesis. Ear protein (Escherichia coli ampicillin resistance) in S. aureus is an exoprotein in COL strain, predicted to be a superantigen, and speculated to play roles in antibiotic resistance and virulence. The goal of this study was to determine if expression of ear is modulated by single nucleotide polymorphisms in its promoter and coding sequences and whether this gene plays roles in antibiotic resistance and virulence. METHODOLOGY: Promoter, coding sequences and expression of the ear gene in clinical and carriage S. aureus strains with distinct genetic backgrounds were analysed. The JE2 strain and its isogenic ear mutant were used in a systemic infection mouse model to determine the competiveness of the ear mutant.Results/Key findings. The ear gene showed a variable expression, with USA300FPR3757 showing a high-level expression compared to many of the other strains tested including some showing negligible expression. Higher expression was associated with agr type 1 but not correlated with phylogenetic relatedness of the ear gene based upon single nucleotide polymorphisms in the promoter or coding regions suggesting a complex regulation. An isogenic JE2 (USA300 background) ear mutant showed no significant difference in its growth, antibiotic susceptibility or virulence in a mouse model. CONCLUSION: Our data suggests that despite being highly expressed in a USA300 genetic background, Ear is not a significant contributor to virulence in that strain.

Role of local allergic inflammation and Staphylococcus aureus enterotoxins in Chinese patients with chronic rhinosinusitis with nasal polyps.

OBJECTIVE: To investigate the role of local allergic inflammation and Staphylococcus aureus enterotoxins in chronic rhinosinusitis with nasal polyps. METHODS: This study included 36 patients with chronic rhinosinusitis with nasal polyps and 18 controls. Total immunoglobulin E, eosinophil cationic protein, staphylococcal enterotoxin types A and B specific immunoglobulin E, staphylococcal enterotoxin types A and B, and myeloperoxidase levels were determined. RESULTS: Four patients with chronic rhinosinusitis with nasal polyps had a local allergy. All chronic rhinosinusitis with nasal polyps patients tested negative for staphylococcal enterotoxin types A and B specific immunoglobulin E. The chronic rhinosinusitis with nasal polyps group had significantly elevated staphylococcal enterotoxin types A and B levels in the supernatant. Fourteen patients belonged to the eosinophilic chronic rhinosinusitis with nasal polyps group and the others were characterised as having non-eosinophilic chronic rhinosinusitis with nasal polyps. CONCLUSION: Local allergy may play a role in chronic rhinosinusitis with nasal polyps, independent of staphylococcal enterotoxin superantigens. Staphylococcal enterotoxins may be important in the pathogenesis of chronic rhinosinusitis with nasal polyps; however, their roles as superantigens were not confirmed in this study. In Chinese subjects, chronic rhinosinusitis with nasal polyps usually manifests as a neutrophilic inflammation.

A novel staphylococcal enterotoxin B subunit vaccine candidate elicits protective immune response in a mouse model.

Staphylococcal enterotoxin B (SEB), produced by the gram-positive bacterium Staphylococcus aureus, is responsible for food poisoning and toxic shock syndrome, and is considered a potential bioterrorism agent. Unfortunately, still now no approved vaccines are available against SEB. In this study, we constructed a series of nontoxic SEB mutants (mSEBs) and examined whether these mSEBs provide protective immunity against SEB challenge. These mSEB vaccine candidates did not demonstrate superantigen activity in mouse splenocyte cultures. Immunization with the vaccine candidates triggered the production of IgG-antibodies with neutralizing activity. In addition, increased production of IgG1 and IgG3 was observed after immunization, which signifies both Th1- and Th2-induced immune responses. Among the vaccine candidates tested, S9, a double mutant (N23A and Y90A) and S19, a quadruple mutant (N23A, Y90A, R110A, and F177A), demonstrated complete protection against a lethal SEB challenge. Altogether, our results strongly suggest that these mSEBs could be an effective recombinant SEB vaccine candidates for further/future preclinical and clinical studies.

Invariant Natural Killer T Cells Are Pathogenic in the HLA-DR4-Transgenic Humanized Mouse Model of Toxic Shock Syndrome and Can Be Targeted to Reduce Morbidity.

During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T -cell response leading to a potentially catastrophic "cytokine storm". Whether innate-like invariant natural killer T (iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B (SEB). Both approaches indicate that iNKT cells are pathogenic in TSS. Importantly, treating DR4tg mice with a TH2-polarizing glycolipid agonist of iNKT cells reduced SEB-inflicted morbidity/mortality. Therefore, iNKT cells may constitute an attractive therapeutic target in superantigen-mediated illnesses.

Localised mitogenic activity in horses following infection with Streptococcus equi.

Streptococcus equi subspecies equi (S. equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S. equi. The aim of this study was to determine the sites of sAg production during infection and therefore improve our understanding of their role. Abscess material, chondroids and serum collected from Equidae with signs of strangles were tested in mitogenic assays. Mitogenic sAg activity was only detected in abscess material and chondroids. Our data support the localised in vivo activity of sAg during both acute and carrier phases of S. equi infection.

Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes.

UNLABELLED: Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens. IMPORTANCE: Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in Staphylococcus aureus colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both in vitro and in vivo. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of S. aureus and its superantigens in the progression to type 2 diabetes.

Low Level of TSST-1 Antibody in Burn Patients With Toxic Shock Syndrome Caused by Methicillin-Resistant Staphylococcus aureus.

Toxic shock syndrome (TSS) caused by methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infection is a growing concern in both adult and pediatric patients. The reason why TSS appears in only some patients with MRSA infection remains unclear. In this study, we analyzed serial TSS toxin-1 (TSST-1) antibody in patients with burn injury to investigate the mechanisms of TSS caused by MRSA nosocomial infection. This study comprised of patients with burn injury in our burn care unit from September, 2010 to August, 2011. Serum samples were collected serially on admission, at 48 to 72 hours after injury, on the day MRSA infection appeared, and on the day MRSA infection resolved. TSST-1 antibody was measured by enzyme-linked immunosorbent assay (ELISA). TSS was diagnosed according to the criteria of the Centers for Disease Control. Serial serum samples were collected from 24 patients and nosocomial MRSA infection was detected in 12 patients. In these 12 patients, TSS occurred in five patients (TSS+ group) but did not occur in the other seven patients (TSS- group). TSST-1 antibody level was significantly lower in the TSS+ group than TSS- group on admission and on the day MRSA infection appeared. All patients in the TSS+ group received intravenous immune globulin when TSS was diagnosed, and no patients died of TSS. Patients suffering from TSS had a lower level of TSST-1 antibody than patients not suffering from TSS. Testing for TSST-1 antibody in the clinical setting might help to predict and prevent the appearance of TSS caused by nosocomial MRSA infection.

Human endogenous retrovirus-K18 superantigen expression and human herpesvirus-6 and human herpesvirus-7 viral loads in chronic fatigue patients.

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex, heterogeneous disease characterized by debilitating fatigue that is not improved with bed rest and worsens after physical activity or mental exertion. Despite extensive research into a cause of CFS, no definitive etiology has been determined; however, a large percentage of CFS patients note an acute infectious event that triggers their fatigue. METHODS: Blood and saliva were collected from 39 CFS cases and 9 healthy control subjects. Peripheral blood mononuclear cells (PBMCs) were tested for human endogenous retrovirus-K18 (HERV-K18) env transcripts using a TaqMan quantitative polymerase chain reaction (qPCR). In addition, viral copy number of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) were measured in both saliva and PBMCs using TaqMan qPCRs. Transcript levels and viral copy number were compared to patient CFS symptom severity. RESULTS: HERV-K18 env transcripts were not significantly different between healthy control subjects and CFS patients. Also, HERV-K18 env transcripts did not correlate with HHV-6 viral copy number or HHV-7 viral copy number in either PBMCs or saliva. HHV-6 viral copy number and HHV-7 viral copy number in both PBMCs and saliva were not significantly different between healthy control subjects and CFS patients. HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number did not correlate with CFS symptom severity. CONCLUSIONS: We fail to demonstrate a difference in HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number between CFS patients and healthy controls. Our data do not support the hypothesis of reactivation of HHV-6 or HHV-7 in CFS.

Methicillin-resistant Staphylococcus aureus-related glomerulonephritis in a child.

BACKGROUND: Methicillin-resistant Staphylococcus aureus-associated glomerulonephritis (MRSA-GN), a syndrome in which superantigens play an important role in the pathogenesis of the infection, has been well described in adult patients but not previously recognized in children. CASE DIAGNOSIS/TREATMENT: We report the case of a 6-year-old girl with MRSA-GN. She presented multiple malformations, including tracheal stenosis necessitating tracheotomy. She was admitted to our hospital because of acute pneumonia caused by a MRSA infection and was found to have proteinuria and abnormal renal function. MRSA was detected in her sputum, and this MRSA isolate produced toxic shock syndrome toxin-1, which acts as a superantigen and stimulates Vß2(+) T cells. A blood test revealed that the number of circulating Vß2(+) T cells expressing CD45RO, a marker of activation, was increased along with a concomitant elevation in the levels of serum immunoglobulins. Both are hallmarks of MRSA-GN. The eradication of MRSA using appropriate antibiotics resulted in the disappearance of the proteinuria; in contrast, corticosteroid treatment failed. To the best of our knowledge, this is the youngest patient to be diagnosed with MRSA-GN. CONCLUSIONS: In summary, there should be a high index of suspicion for MRSA-GN, even in the very young, in order to avoid the unnecessary use of immune suppressants in this context.

Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma.

BACKGROUND: The role of IgE in patients with severe asthma is not fully understood. OBJECTIVE: We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease severity in adult asthmatic patients. METHODS: Specific IgE antibody concentrations in serum against enterotoxins, grass pollen (GP), and house dust mite allergens and total IgE levels were measured in adult cohorts of 69 control subjects, 152 patients with nonsevere asthma, and 166 patients with severe asthma. Severe asthma was defined as inadequately controlled disease despite high-dose inhaled corticosteroids plus at least 2 other controller therapies, including oral steroids. RESULTS: Enterotoxin IgE positivity was significantly greater in patients with severe asthma (59.6%) than in healthy control subjects (13%, P< .001). Twenty-one percent of patients with severe asthma with enterotoxin IgE were considered nonatopic. Logistic regression analyses demonstrated significantly increased risks for enterotoxin IgE-positive subjects to have any asthma (OR, 7.25; 95% CI, 2.7-19.1) or severe asthma (OR, 11.09; 95% CI, 4.1-29.6) versus enterotoxin IgE-negative subjects. The presence of GP or house dust mite IgE antibodies was not associated with either significantly increased risk for asthma or severity. Oral steroid use and hospitalizations were significantly increased in patients with enterotoxin IgE and nonatopic asthma. GP IgE was associated with a higher FEV(1) percent predicted value, and enterotoxin IgE was associated with a lower FEV(1) percent predicted value. CONCLUSIONS: Staphylococcal enterotoxin IgE antibodies, but not IgE against inhalant allergens, are risk factors for asthma severity. We hypothesize that the presence of enterotoxin IgE in serum indicates the involvement of staphylococcal superantigens in the pathophysiology of patients with severe asthma.

Chronic rhinosinusitis and asthma: novel understanding of the role of IgE 'above atopy'.

Chronic rhinosinusitis (CRS) affects more than 10% of the European population and is often associated with asthma. Phenotypes of CRS can be differentiated based on mucosal remodelling and inflammatory patterns. Understanding the role of central mediators, such as interleukin-5, in these different phenotypes may lead to the development of specific therapeutic approaches. The impact of staphylococcal superantigens has been shown to further modify the immune response, contributing to persistent severe disease via the activation of T and B cells and the formation of local IgE. It is clear that these mechanisms are involved in the systemic spread of upper airway disease with resulting asthma comorbidity, when IgE antibodies to staphylococcal enterotoxins are present at measurable levels in serum. Recent findings point to superantigens as possible causal agents in the intrinsic form of severe asthma, and an anti-IgE strategy has shown promising therapeutic potential in nonatopic patients with nasal polyps and asthma. These findings should lead to a clinically relevant endotyping of patients with upper and lower airway disease and to a new understanding of the role of IgE 'above atopy'.

Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children.

Children with burns have a greater risk of developing toxic shock syndrome (TSS) than adults. This risk is thought to be associated with colonisation by toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus in children with insufficient antibody titers. The diagnosis of TSS is difficult because, in the early stages, its signs and symptoms resemble those of other common childhood illnesses such as scarlet fever. If the condition is not treated promptly, the mortality rate is high. This study was designed to determine the titers of TSST-1 serum antibody in Japanese children, in order to prevent TSS and facilitate its early diagnosis. Between May 2006 and May 2007, we studied 119 patients who were treated in the Department of Plastic and Reconstructive Surgery of Kanazawa Medical University Hospital. An enzyme-linked immunosorbent assay (ELISA) was used to test the level of the IgG antibody to TSST-1 in the patients' serum samples. The percentage of cases testing for TSST-1 antibody in the patients under 6 months old was 78.6%, and it was lowest (21.3%) in the age group from 6 to 12 months old. The group of patients older than 41 years showed the highest rate of positivity (100.0%) for TSST-1 antibody. Higher titers of TSST-1 antibody were found within the first 6 months after birth, and lower titers were found between 6 months and 2 years old. The titers began to increase again after age three. The high morbidity of TSS in children around 2 years of age was proven to be related to changes in the titers of TSST-1 antibody. Infants under 6 months old are protected from TSS because of the high level of TSST-1 antibody they receive from their mother. Children are at risk of developing staphylococcal toxic shock syndrome when their immune system is immature and they have no protective circulating anti-TSS antibodies.

Late-onset of IgE sensitization to microbial allergens in young children with atopic dermatitis.

Background A significant proportion of young children with atopic dermatitis (AD) is sensitized to microbial allergens, which play a potential role in the pathogenesis of AD inflammation. Objective To study the timing of IgE sensitization to microbial allergens including staphylococcal superantigens, Malassezia species and Candida albicans in young children with AD. Method Specific IgE antibodies to staphylococcal superantigens, Malassezia species, C. albicans and control inhalant/food allergens were measured in 53 young children with mild to moderate AD. The presence of IgE sensitization relative to age (> or = 3 years vs. < 3 years) was analysed by logistic regressions. Results IgE sensitization to the staphylococcal superantigen group, Malassezia species and C. albicans was significantly associated with older age in children with AD [P = 0.02, odds ratio (OR) 4.9; P = 0.02, OR 4.7; and P = 0.05, OR 4.0, respectively]. Conclusion IgE sensitization to microbial allergens is associated with an older age group in young children with mild to moderate AD.

Severe group A streptococcal infections in Uppsala County, Sweden: clinical and molecular characterization of a case cluster from 2006 to 2007.

This study describes a recent cluster of 30 patients (median age 52 years) with serious group A streptococcal (GAS) infections in Uppsala County, Sweden, from December 2006 to May 2007. Patients hospitalized with a severe GAS infection, i.e. cases with either invasive GAS (iGAS) disease or patients with a positive non-sterile site culture/rapid antigen test for GAS and clinically considered as having a critical disease, were included in the study. Common clinical presentations were skin and soft tissue infections (53%) and pneumonia (17%). Eight patients (27%) were diagnosed with streptococcal toxic shock syndrome. In 40% of the cases no relevant underlying disease was reported. Among the 16 patients with soft tissue infections, the upper chest, neck or upper arm area was frequently affected and the infection was associated with severe pain. Among the 20 collected isolates, the T1/emm1 type dominated (80%). The majority (86%) of 7 analysed acute sera lacked neutralizing activity against superantigens produced by the patients' own infecting isolate. The study underscores the association between T1/emm1 and outbreaks of serious GAS infections. This highlights the importance of surveillance for prompt identification of more aggressive isolates in the community, thereby increasing awareness among healthcare professionals of these life-threatening infections.

Serological responses to microbial antigens in celiac disease patients during a gluten-free diet.

BACKGROUND: Immunoglobulin A (IgA) autoantibodies to tissue transglutaminase (tTG) are commonly used for screening and diagnosing of celiac disease (CD). Seroreactivity for anti-Saccharomyces cerevisiae antibody (ASCA) and bacterial antigens have also been detected in CD patients. The aim of this study was to examine prospectively serologic responses to microbial targets in adult CD patients at the time of diagnosis and during a gluten-free diet (GFD). Further, we wanted to evaluate whether these serologic specificities could provide new tools for the follow-up of CD patients. METHODS: Data on 55 adult biopsy-proven CD patients were available for follow-up study. Upper gastrointestinal endoscopy was performed on all patients. Sera from patients were tested for antibodies to tTG and ASCA and additionally analyzed with IgA enzyme-linked immunosorbent assays to Pseudomonas fluorescens-associated sequence, I2, and to a Bacteroides caccae TonB-linked outer membrane protein, OmpW. RESULTS: At the time of diagnosis, 91% of CD cases were positive for tTG and 49% for ASCA; positive seroreactivity to I2 was found in 86% and to OmpW in 60% of CD patients at the time of diagnosis. The frequency of seropositivity and serum levels of these antibodies decreased during GFD. Moreover, we found that the decline in the serum levels was significant in all of these markers (p < 0.005). Interestingly, we also found that serum levels of ASCA correlated with the grade of mucosal morphology (p = 0.021), as the ASCA serum levels declined in accordance with mucosal healing. CONCLUSIONS: Commensal enteric bacteria seem to play a role in the small intestinal mucosal damage in CD. This was proven by the serological responses to different microbial antigens shown in this study. Serum levels of ASCA, anti-I2, and anti-OmpW antibodies decreased significantly during GFD, indicating that these serologic markers are gluten dependent in CD patients. These specificities could provide new tools in the follow-up of CD patients.

Sepsis strategies in development.

Severe sepsis, defined as inflammation and organ failure due to infection, continues to result in a mortality of approximately 30% despite advances in critical care. Current therapy includes timely administration of antibiotics, source control of infection, aggressive fluid resuscitation, support of failing organs, and use of activated protein C where clinically indicated. Bacterial mediators, including endotoxin and superantigens, as well endogenous proinflammatory cytokines are considered important to the pathogenesis of sepsis-induced organ failure and are being targeted with numerous molecules and removal devices. Additional therapeutic strategies are aimed at restoring the natural anticoagulant levels, blocking deleterious effects of the complement cascade, reversing cytopathic hypoxia, and inhibiting excessive lymphocyte apoptosis. Molecules with pluripotent activity, such as interalpha inhibitor proteins and estrogen-receptor ligands, are also being investigated.

Association of staphylococcal superantigen-specific immunoglobulin e with mild and moderate atopic dermatitis.

OBJECTIVE: To examine the frequency of allergic sensitization to staphylococcal superantigens in young children with mild to moderate atopic dermatitis (AD). STUDY DESIGN: AD severity was assessed with objective Scoring AD. Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1 were measured with ImmunoCAP. Comparisons between mild AD and moderate AD were performed by using logistic regressions. RESULTS: The prevalence of allergic sensitization to staphylococcal superantigens in patients with mild and moderate AD was 38% and 63%, respectively. Allergic sensitization to staphylococcal superantigens, particularly SEA and SED, was found to be associated with moderate AD, compared with mild AD. CONCLUSIONS: Our results suggest that allergic sensitization to staphylococcal superantigens is common even in young children with mild to moderate AD, and such sensitization may contribute to the disease severity of these patients.

Membranoproliferative glomerulonephritis in patients with cystic fibrosis: coincidence or comorbidity? A case series.

Cystic fibrosis (CF) is perceived as a childhood illness. However, with advances in medical science, patients are enjoying lives extending well into adulthood. This article reviews two cases of membranoproliferative glomerulonephritis (MPGN) in adults with CF. One patient with severe CF pulmonary disease had concomitant renal failure during hospitalization for a pulmonary exacerbation. Subsequent evaluations, including complement levels, were consistent with MPGN. The second patient had been recently diagnosed with colon cancer and was found to be suffering from acute renal failure. Diagnostic evaluation likewise confirmed the MPGN diagnosis. Immunologic associations linking CF and MPGN, including derangements in the complement system and the effects of superantigen production, are reviewed.

Analysis of superantigenic toxin Vbeta T-cell signatures produced during cases of staphylococcal toxic shock syndrome and septic shock.

Most clinical isolates of Staphylococcus aureus harbour genes encoding superantigenic toxins that bind the Vbeta domain of T-cells, but little information is available concerning superantigenic toxin production during staphylococcal toxic shock syndrome (TSS) and septic shock. This prospective study investigated 14 patients with staphylococcal TSS or septic shock; the toxin gene profile of each isolate was determined and flow-cytometry was used to identify the discriminant Vbeta signature (DVbetaS) of each superantigenic toxin in vitro. Attempts were also made to identify in-vivo production of superantigenic toxin DVbetaS in patients' blood. The DVbetaS identified in vitro were: toxic shock syndrome toxin (TSST)-1, Vbeta 2; staphylococcal enterotoxin (SE), Vbeta 9, Vbeta 22; SEB, Vbeta 3, Vbeta 14, Vbeta 17; SED, Vbeta 1, Vbeta 8; egc, Vbeta 5.3, Vbeta 7.1, Vbeta 9, Vbeta 23; and SElK, Vbeta 5.1. The DVbetaS of TSST-1 and SEB were detected in patients with menstrual and non-menstrual TSS, respectively, whereas no Vbeta signature was detected during septic shock. All patients with septic shock (but only one patient with TSS) had lymphopenia and/or impaired cellular immunity. Detection of a superantigenic toxin DVbetaS may help to show which toxin is produced during staphylococcal TSS, thus confirming the diagnosis and hastening the administration of anti-toxin therapy. In contrast, this approach failed to demonstrate superantigenic toxin involvement in cases of septic shock. In this latter condition, a superantigenic toxin may not be produced by S. aureus, or its production may occur without expansion of targeted T-cells because of T-cell apoptosis and/or anergy.