High-sensitivity monoclonal antibodies specific for homoserine lactones protect mice from lethal Pseudomonas aeruginosa infections.

A number of bacteria, including pathogens like Pseudomonas aeruginosa, utilize homoserine lactones (HSLs) as quorum sensing (QS) signaling compounds and engage in cell-to-cell communication to coordinate their behavior. Blocking this bacterial communication may be an attractive strategy for infection control as QS takes a central role in P. aeruginosa biology. In this study, immunomodulation of HSL molecules by monoclonal antibodies (MAbs) was used as a novel approach to prevent P. aeruginosa infections and as tools to detect HSLs in bodily fluids as a possible first clue to an undiagnosed Gram-negative infection. Using sheep immunization and recombinant antibody technology, a panel of sheep-mouse chimeric MAbs were generated which recognized HSL compounds with high sensitivity (nanomolar range) and cross-reactivity. These MAbs retained their nanomolar sensitivity in complex matrices and were able to recognize HSLs in P. aeruginosa cultures grown in the presence of urine. In a nematode slow-killing assay, HSL MAbs significantly increased the survival of worms fed on the antibiotic-resistant strain PA058. The therapeutic benefit of these MAbs was further studied using a mouse model of Pseudomonas infection in which groups of mice treated with HSL-2 and HSL-4 MAbs survived, 7 days after pathogen challenge, in significantly greater numbers (83 and 67%, respectively) compared with the control groups. This body of work has provided early proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as theranostic clinical leads suitable for the diagnosis, prevention, and treatment of life-threatening bacterial infections.

Global prevalence of ankylosing spondylitis.

OBJECTIVES: For effective health care provision, knowledge of disease prevalence is paramount. There has been no systematic endeavour to establish continent-based AS estimates, however, prevalence is thought to vary by country and background HLA-B27 prevalence. This study aimed to estimate AS prevalence worldwide and to calculate the expected number of cases. METHODS: A systematic literature search was conducted. Prevalence data were extracted and used to calculate the mean prevalence by continent and the expected number of cases based on country-specific prevalence (or, if missing, the prevalence from neighbouring countries). A second estimate was made using the prevalence from countries with similar HLA-B27 prevalences if a country-specific prevalence estimate was not available. RESULTS: The mean AS prevalence per 10,000 (from 36 eligible studies) was 23.8 in Europe, 16.7 in Asia, 31.9 in North America, 10.2 in Latin America and 7.4 in Africa. Additional estimates, weighted by study size, were calculated as 18.6, 18.0 and 12.2 for Europe, Asia and Latin America, respectively. There were sufficient studies to estimate the number of cases in Europe and Asia, calculated to be 1.30-1.56 million and 4.63-4.98 million, respectively. CONCLUSION: This study represents the first systematic attempt to collate estimates of AS prevalence into a single continent-based estimate. In addition, the number of expected cases in Europe and Asia was estimated. Through reviewing the current literature, it is apparent that the continuing conduct of epidemiological studies of AS prevalence is of great importance, particularly as diagnostic capabilities improve and with the recent development of the criteria for axial SpA.

Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK primary care case-control study.

BACKGROUND: Infectious mononucleosis (IM) and vitamin D deficiency are both risk factors for multiple sclerosis (MS). OBJECTIVE: We wished to establish if IM in the winter months when vitamin D levels are low may be a greater risk factor for MS than IM in the summer months. METHODS: We identified all patients with MS diagnosed aged 16-60 in a large primary care database in the United Kingdom and matched each by age, sex, general practice and observation period with up to six controls. We identified a coded diagnosis of IM prior to the index date (date of diagnosis). Logistic regression was used to calculate the odds ratio for prior IM exposure in cases versus controls and for winter versus summer exposure in cases and controls with prior IM exposure. RESULTS: Based on 9247 cases and 55,033 matched controls (246 and 846 with prior IM respectively), IM was associated with the development of MS (OR 1.77, 95%CI 1.53-2.05) but there was no evidence that IM in the winter as opposed to summer was associated with developing MS (OR 1.09, 95%CI 0.72-1.66). CONCLUSION: We found no evidence that the season of IM influences the risk of subsequent MS.