Long-Term Sinonasal Carriage of Staphylococcus aureus and Anti-Staphylococcal Humoral Immune Response in Patients with Chronic Rhinosinusitis

We investigated Staphylococcus aureus diversity, genetic factors, and humoral immune responses against antigens via genome analysis of S. aureus isolates from chronic rhinosinusitis (CRS) patients in a long-term follow-up. Of the 42 patients who provided S. aureus isolates and serum for a previous study, 34 could be included for follow-up after a decade. Clinical examinations were performed and bacterial samples were collected from the maxillary sinus and nares. S. aureus isolates were characterized by whole-genome sequencing, and specific anti-staphylococcal IgG in serum was determined using protein arrays. S. aureus was detected in the nares and/or maxillary sinus at both initial inclusion and follow-up in 15 of the 34 respondents (44%). Three of these (20%) had S. aureus isolates from the same genetic lineage as at inclusion. A low number of single-nucleotide polymorphisms (SNPs) were identified when comparing isolates from nares and maxillary sinus collected at the same time point. The overall change of antibody responses to staphylococcal antigens over time showed great variability, and no correlation was found between the presence of genes encoding antigens and the corresponding anti-staphylococcal IgG in serum; thus our findings did not support a role, in CRS, of the specific S. aureus antigens investigated

Long-term sinonasal carriage of staphylococcus aureus and anti-staphylococcal humoral immune response in patients with chronic rhinosinusitis

We investigated Staphylococcus aureus diversity, genetic factors, and humoral immune responses against antigens via genome analysis of S. aureus isolates from chronic rhinosinusitis (CRS) patients in a long-term follow-up. Of the 42 patients who provided S. aureus isolates and serum for a previous study, 34 could be included for follow-up after a decade. Clinical examinations were performed and bacterial samples were collected from the maxillary sinus and nares. S. aureus isolates were characterized by whole-genome sequencing, and specific anti-staphylococcal IgG in serum was determined using protein arrays. S. aureus was detected in the nares and/or maxillary sinus at both initial inclusion and follow-up in 15 of the 34 respondents (44%). Three of these (20%) had S. aureus isolates from the same genetic lineage as at inclusion. A low number of single-nucleotide polymorphisms (SNPs) were identified when comparing isolates from nares and maxillary sinus collected at the same time point. The overall change of antibody responses to staphylococcal antigens over time showed great variability, and no correlation was found between the presence of genes encoding antigens and the corresponding anti-staphylococcal IgG in serum; thus our findings did not support a role, in CRS, of the specific S. aureus antigens investigated

Caries risk assessment in school children using a reduced Cariogram model without saliva tests

<p>Abstract</p> <p>Background</p> <p>To investigate the caries predictive ability of a reduced Cariogram model without salivary tests in schoolchildren.</p> <p>Methods</p> <p>The study group consisted of 392 school children, 10-11 years of age, who volunteered after informed consent. A caries risk assessment was made at baseline with aid of the computer-based Cariogram model and expressed as "the chance of avoiding caries" and the children were divided into five risk groups. The caries increment (ΔDMFS) was extracted from the dental records and bitewing radiographs after 2 years. The reduced Cariogram was processed by omitting the variables "salivary mutans streptococci", "secretion rate" and "buffer capacity" one by one and finally all three. Differences between the total and reduced models were expressed as area under the ROC-curve.</p> <p>Results</p> <p>The baseline caries prevalence in the study population was 40% (mean DMFS 0.87 ± 1.35) and the mean 2-year caries increment was 0.51 ± 1.06. Both Cariogram models displayed a statistically relationship with caries development (p < 0.05); more caries was found among those assessed with high risk compared to those with low risk. The combined sensitivity and specificity decreased after exclusion of the salivary tests and a statistically significant reduction of the area under the ROC-curve was displayed compared with the total Cariogram (p < 0.05). Among the salivary variables, omission of the mutans streptococci enumeration impaired the predictive ability the most.</p> <p>Conclusions</p> <p>The accuracy of caries prediction in school children was significantly impaired when the Cariogram model was applied without enumeration of salivary tests.</p

Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment

Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10−5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10−8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05–2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema

Invasive haemophilus influenzae infection. Clinical, immunologic and pathogenic aspects

Invasive Haemophilus influenzae (Hi) infection, predominantly manifested as acute meningitis and epiglottitis, is a serious disease with associated mortality and residual handicap. Prevention of the disease is possible by vaccination against Hi serotype b (Hib). In a prospective study in a Swedish population before large scale Hib vaccination of infants was introduced, the incidence of invasive Hi infection, in children 0-4 years of age, was 55/100.000/year. Hib caused 98 % of the cases. In a study on laboratory reports, the incidence in Sweden was reduced by 90 % two years after the initiation of the vaccination programme. The pre vaccination incidence in adults was high; 2.8/100.000/year and 51% of the cases were caused by Hib. No significant impact on the incidence in children older than 4 years and adults was found by the vaccination programme during the first two years. Acute epiglottitis during the pre vaccination era was studied retrospectively, and the incidence was higher than previously reported. Blood cultures confirmed Hi as the most prevalent etiologic pathogen in children, but in adult epiglottitis, the aetiology was often unknown. Cultures from nasopharynx had a low diagnostic value. The case fatality rate of invasive Hi infection was 2.9 % and residual sequelae were diagnosed in 5.8 %. These cases were all caused by Hib. The most prevalent sequelae was sensorineural hearing loss after meningitis. Adults who had recovered from Hi meningitis in childhood were investigated and the prevalence of a late progression of pure tone audiometric abnormality was documented. In these cases, hearing loss was peripheral, with cochlea as the suspected site of the lesion, and subclinical vestibular pathology was over-represented. However, brain dysfunction and central auditory disturbance, unpredictable by conventional audiometry was also found. The functional capacity of Hib vaccination induced antibodies was studied with three assays. The induced serum bactericidal and opsonophagocytic activity usually correlated to the serum concentration of antibodies against the Hib capsular polysaccharide (PRP). However, the prevalence of non-functional antibodies indicates that a functional evaluation is desirable in addition to serum concentrations of antibodies in bacterial vaccine trials. A chemiluminescence (CL)-index assay proved more useful than phagocytic killing in measuring serum opsonic action, and the ELISA and CL-index showed that PRP conjugated to diphtheria toxoid was more immunogenic than PRP conjugated to outer membrane protein complex of meningococcus serogroup B. In an overlay assay of radiolabeled bacteria by thin-layer chromatography, Hi recognised three glycosphingolipid (GSL) specificities; lactosylceramide, gangliotri-/gangliotetraosylceramide and neolactotetraosylceramide. Target tissues for Hi were investigated for relevant GSLs and Hi bound to neolactotetraosylceramide of polymorphonuclear leukocytes and oropharyngeal epithelium. The epithelial expression of neolactotetraosylceramide, although as a minor compound, serve as a relevant carbohydrate receptor for Hi in the upper respiratory tract

Anti-Staphylococcal Humoral Immune Response in patients with chronic rhinosinusitis

Background: Staphylococcus aureus (S. aureus) can behave both as a harmless commensal and as a pathogen. Its significance in the pathogenesis of chronic rhinosinusitis (CRS) is not yet fully understood. This study aimed to determine serum antibody responses to specific staphylococcal antigens in patients with CRS and healthy controls, and to investigate the correlation between specific antibody response and severity of symptoms. Methodology: Serum samples from 39 patients with CRS and 56 healthy controls were analysed using a protein microarray to investigate the antibody response to S. aureus specific antigens, with a focus on immunoglobulin G (IgG) directed toward staphylococcal components accessible to the immune system. Holm-Bonferroni corrections were applied in all analyses. Information about growth of S. aureus in nares and maxillary sinus was taken from a previous study based on the same individuals. Clinical symptoms were assessed using a scoring system. Results: IgG antibody levels toward staphylococcal TSST-1 and LukF-PV were significantly higher in the CRS patient group compared to healthy controls, and levels of anti-TSST-1 antibodies were significantly higher in the CRS patient group with S. aureus in maxillary sinus than in controls. There were no correlations between the severity of symptoms and levels of serum anti-staphylococcal IgG antibody levels for LukF-PV and TSST-1. Conclusions: TSST-1 and LukF-PV could be interesting markers for future studies of the pathogenesis of CRS