[Precision medicine in infectious diseases]. / Präzisionsmedizin in der Infektiologie.

Infectious medicine faces a variety of challenges, such as the increase in antibiotic resistance and the emergence and spread of infectious diseases fueled by climate change and globalization. Precision medicine can provide solutions to many of these challenges. Since an untargeted request for diagnostic tests can lead to test results without clinical relevance, which can increase the use of non-indicated antibiotics, the principle aimed at is: targeted diagnostics (the right test) and consideration of patient characteristics (the right person) to optimize management (the right action). At the same time, one must always decide whether empirical therapy must be immediately initiated, even if the results of the initiated diagnostics are not yet available. In addition, many new diagnostics as well as therapies have recently been developed for the rapid detection and more specific treatment of bacterial infections. Molecular genetic methods, which offer more rapid results than classical bacterial cultures, are gaining ground as new diagnostics. New therapeutics such as bacteriophages, antibodies or antibacterial peptides allow increasingly precise treatment of certain bacterial infections. Precision medicine will also play an increasingly important role in infectious medicine in the future.

Association between the quality of plant-based diets and periodontitis in the U.S. general population.

AIM: To investigate the relationship between plant-based diet indices (PDIs) and periodontitis and serum IgG antibodies against periodontopathogens in the U.S. MATERIALS AND METHODS: We analysed cross-sectional data on 5651 participants ≥40 years of age from the Third National Health and Nutrition Examination Survey. Food frequency questionnaire data were used to calculate the overall PDI, healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Periodontitis was defined using a half-reduced Centers for Disease Control and Prevention and American Academy of Periodontology case definition. Serum antibodies against 19 periodontopathogens were used to classify the population into two subgroups using hierarchical clustering. Survey-weighted multivariable logistic regressions were applied to assess the associations of PDI/hPDI/uPDI z-scores with periodontitis and hierarchical clusters after adjusting for potential confounders. RESULTS: A total of 2841 (50.3%) participants were defined as having moderate/severe periodontitis. The overall PDI z-score was not significantly associated with the clinical and bacterial markers of periodontitis. By considering the healthiness of plant foods, we observed an inverse association between hPDI z-score and periodontitis (odds ratio [OR] = 0.925, 95% confidence interval [CI]: 0.860-0.995). In contrast, higher uPDI z-score (adherence to unhealthful plant foods) might increase the risk of periodontitis (OR = 1.100; 95% CI: 1.043-1.161). Regarding antibodies against periodontopathogens, the participants in cluster 2 had higher periodontal antibodies than those in cluster 1. The hPDI z-score was positively associated with cluster 2 (OR = 1.192; 95% CI: 1.112-1.278). In contrast, an inverse association between uPDI z-score and cluster 2 was found (OR = 0.834; 95% CI: 0.775-0.896). CONCLUSIONS: Plant-based diets were associated with periodontitis, depending on their quality. A healthy plant-based diet was inversely related to an increased risk of periodontitis but positively related to elevated antibody levels against periodontopathogens. For an unhealthy plant-based diet, the opposite trends were observed.

Age and gender associated changes in immunoglobulin subclass levels specific to S. pneumoniae, serotype 1.

S. pneumoniae is an important human pathogen which has a polysaccharide capsule with virulent properties. This work aims to estimate the titres of S. pneumoniae specific IgG and IgA isotypes, with respect to age and sex. An in-house whole bacterial cell ELISA was used for the determination of relative levels and endpoint titres of IgG subclasses and IgA1 subclass specific for S. pneumoniae serogroup 1, and to quantify specific IgG1 and IgG2 levels. Significantly lower anti-pneumococcus IgG1 titres were found in older individuals, which was more pronounced in men. Lower IgG2 titres were detected in men over 50 years of age, in comparison to women under 50 years of age. The levels of IgG3 and IgG4 did not differ between different sex and age groups. Lower IgA1 levels were detected in male individuals in both age groups in comparison to females under 50 years of age. The levels of IgG1 showed a moderate correlation with IgG4 in younger individuals of both sexes (r = 0.61 in men and 0.63 in women) which was not noted in the older age group. We highlight the deficiency in humoral immunity in older people, especially male and suggest immunization of this population with pneumococcal vaccines.

Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies.

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently, Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence of E. gallinarum exposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarum IgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarum antibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive with E. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarum IgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarum titers were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarum titers correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive to E. gallinarum. In SLE patients, the immune response to E. gallinarum was associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence that E. gallinarum may be a pathobiont for SLE in susceptible individuals.

Serum IgG Antibodies against Periodontal Microbes and Cancer Mortality.

INTRODUCTION: Periodontitis is a chronic inflammatory condition initiated by microorganisms and is positively linked to systemic conditions such as cancer, cardiovascular disease, and diabetes mellitus. OBJECTIVES: To prospectively investigate associations between empirically derived clusters of IgG antibodies against 19 selected periodontal microorganisms and cancer mortality in a representative sample of the US population. METHODS: We evaluated 6,491 participants aged ≥40 y from the Third National Health and Nutrition Examination Survey (1988 to 1994), who had complete data on IgG antibody titers against 19 selected periodontal microorganisms and were free of cardiovascular disease and cancer. In a prior study, antibodies were categorized into 4 mutually exclusive groups via cluster analysis: red-green, orange-red, yellow-orange, and orange-blue. Cluster scores were estimated by summing z scores of the antibody titers making up each cluster. Participants were followed up to death until December 31, 2011. Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% CIs for all-cancer mortality by tertiles of cluster scores. RESULTS: During follow-up for a median of 15.9 y, there were 2,702 deaths (31.3%), including 631 cancer-related deaths (8.1%). After adjusting for multiple confounders, the orange-blue cluster was inversely associated with cancer mortality (tertile 2 vs. tertile 1: HR = 0.67, 95% CI = 0.54 to 0.84; tertile 3 vs tertile 1: HR = 0.62, 95% CI = 0.46 to 0.84). The association between the yellow-orange cluster and all-cancer mortality was also inverse but not significant, and the orange-red cluster and the red-green cluster were not associated with all-cancer mortality. CONCLUSIONS: Antibodies against Eubacterium nodatum and Actinomyces naeslundii may be novel predictors of cancer mortality. If further studies establish a causal relationship between these antibodies and cancer mortality, they could be targets to prevent possible systemic effects of periodontal disease with potential interventions to raise their levels. KNOWLEDGE TRANSFER STATEMENT: Periodontal antibodies against Eubacterium nodatum and Actinomyces naeslundii were inversely associated with cancer mortality among adults followed up for an average of 16 y. Periodontal antibodies may predict cancer mortality.

Mycoplasma pneumoniae outbreak, Southeastern Finland, 2017-2018: molecular epidemiology and laboratory diagnostic lessons.

This study characterizes a large Mycoplasma pneumoniae outbreak observed in Kymenlaakso in Southeastern Finland during August 2017-January 2018. The first part of the investigation included 327 patients, who sought healthcare consultation at local GPs or hospitals due to clinical symptoms, and were tested for M. pneumoniae antibodies (Patient cohort). The second part of the investigation, conducted approximately 4 weeks after the peak of the outbreak, consisted of school screening of pupils (N = 239) in three different school buildings by PCR on respiratory specimens and questionnaires (Screening cohort). PCR positive respiratory specimens were subsequently utilized for molecular typing. The outbreak peaked in late October 2017. Of the Patient cohort, 9/106 (8.5%) respiratory specimens were PCR positive. In contrast, 3/182 (1.6%) of the Screening cohort were PCR positive. Asymptomatic carriage was observed. Multiple-locus variable-number tandem-repeat analysis (MLVA) identified two distinct MLVA types. All typed M. pneumoniae strains belonged to P1 type 1. No mutations leading to macrolide resistance were observed. In total, 61/327 (19%) of the Patient cohort had a serological indication of recent infection. The IgM test reactivity at the time of a negative PCR test result varied from a completely non-reactive value up to very strong reactivity, highlighting the difficulty in a single specimen serodiagnosis.

Correlation of natural autoantibodies and cardiovascular disease-related anti-bacterial antibodies in pericardial fluid of cardiac surgery patients.

Our previous studies showed that anti-citrate synthase (anti-CS) immunoglobulin (Ig)M natural autoantibodies are present in healthy individuals without previous antigen stimulation, but no studies have investigated their presence in the pericardial fluid (PF). Therefore, we detected the natural anti-CS IgG/M autoantibody levels in plasma and PF of cardiac surgery patients and investigated their relationship with cardiovascular disease-associated bacterial pathogens. PF and blood samples of 22 coronary artery bypass graft (CABG) and 10 aortic valve replacement (AVR) patients were tested for total Ig levels, natural autoantibodies and infection-related antibodies using enzyme-linked immunosorbent assay (ELISA) and Luminex methods. The B cell subsets were measured by flow cytometry. The total Ig subclass levels were four to eight times lower in PF than in plasma, but the natural anti-CS IgM autoantibodies showed a relative increase in PF. The frequency of CD19+ B lymphocytes was significantly lower in PF than in blood (P = 0·01), with a significant relative increase of B1 cells (P = 0·005). Mycoplasma pneumoniae antibody-positive patients had significantly higher anti-CS IgM levels. In CABG patients we found a correlation between anti-CS IgG levels and M. pneumoniae, Chlamydia pneumoniae and Borrelia burgdorferi antibody titres. Our results provide the first evidence that natural autoantibodies are present in the PF, and they show a significant correlation with certain anti-bacterial antibody titres in a disease-specific manner.

Human seroreactivity to gut microbiota antigens.

BACKGROUND: Although immune responses directed against antigens from the intestinal microbiota are observed in certain diseases, the normal human adaptive immune response to intestinal microbiota is poorly defined. OBJECTIVE: Our goal was to assess the adaptive immune response to the intestinal microbiota present in 143 healthy adults and compare this response with the response observed in 52 children and their mothers at risk of having allergic disease. METHODS: Human serum was collected from adults and children followed from birth to 7 years of age, and the serum IgG response to a panel of intestinal microbiota antigens was assessed by using a novel protein microarray. RESULTS: Nearly every subject tested, regardless of health status, had serum IgG that recognized a common set of antigens. Seroreactivity to the panel of antigens was significantly lower in atopic adults. Healthy infants expressed the highest level of IgG seroreactivity to intestinal microbiota antigens. This adaptive response developed between 6 and 12 months of age and peaked around 2 years of age. Low IgG responses to certain clusters of microbiota antigens during infancy were associated with allergy development during childhood. CONCLUSIONS: There is an observed perturbation of the adaptive response to antigens from the microbiota in allergic subjects. These perturbations are observable even in childhood, suggesting that optimal stimulation of the adaptive immune system by the microbiota might be needed to prevent certain immune-mediated diseases.

Application of egg-yolk-antibody to prevent recolonization of Streptococcus mutans / 实用口腔医学杂志

Objective:To investigate the effect of local application of the water soluble protein fraction,containing specific egg yolk antibody,on the recolonization of Streptococcus mutans.Methods:Whole cells of inactivated streptococcus mutans were used as antigen to immunize bens,then water soluble protein fraction(WSF) was extracted from the eggs. Mouth wash containing 0.1 mg/ml of WSF was prepared and administered to 8 volunteers.The mouth wash was used once every two days for 2 weeks.Vehicle solution was used in other 6 volunteers as the control.S.mutans in saliva was monitored for 100 days.Results:Before using the mouth washes,S.mutans level in saliva of the volunteers was 36.4%.S.mutans was removed by hibitane,it kept less than 3% in 100 days in the tested individuals,while 23%～37% in the controls.Conclusion:The WSF containing specific egg yolk antibody can effectively prevent the recolonization of streptococcus mutans.