CD18 mediates neutrophil imperviousness to the Aggregatibacter actinomycetemcomitans JP2 clone in molar-incisor pattern periodontitis

INTRODUCTION: Molar-incisor pattern periodontitis (MIPP) in the absence of significant local risk factors or systemic disease, is a rare, early onset periodontal disease phenotype, with 0.5% to 2.5% global prevalence. The condition is characterized by impaired neutrophil function and persistent Aggregatibacter actinomycetemcomitans (JP2 clone) infection. The aim of this study was to characterize neutrophil functional responses to JP2 and to investigate the neutrophil receptors involved. MATERIALS AND METHODS: Neutrophils were obtained from whole blood samples of periodontally healthy and MIPP subjects and incubated with the JP2 clone or a non-JP2 clone of A. actinomycetemcomitans. Bacterial survival was tested by blood agar culture; neutrophil death was tested with propidium iodide and flow cytometry; Reactive oxygen production (ROS) was measured with 2′,7′-dichlorofluorescein diacetate and a fluorescence plate reader; the cytokinome was analysed using an array profiler, ELISA and RT-PCR. Receptors binding to JP2 were isolated using a novel immunoprecipitation assay and validated functionally using specific blocking antibodies. RESULTS: JP2 and non-JP2 survival was comparable between all the neutrophil groups. Resistance to neutrophil necrosis following exposure to JP2 was significantly lower in the MIPP group, than in all the other groups (p<0.0001). Conversely, MIPP neutrophils showed lower levels of ROS production in response to JP2 infection compared with that of healthy neutrophils (p<0.001). Furthermore, significantly lower levels of cytokines, such as IL8, IL10 and TNFα, were observed during JP2 incubation with MIPP neutrophils than upon incubation with periodontally healthy neutrophils. Various proteins expressed on neutrophils bind to JP2. Of these, CD18 was found to mediate neutrophil necrosis. The CD18 receptor on MIPP neutrophils acts differently from that on periodontally healthy patients neutrophils, and appears to reflect differential neutrophil reactions to JP2. CONCLUSION: This study portrays a fundamental difference in neutrophil response to JP2 infection between periodontally healthy and MIPP patients. This was evident in the resistance to necrosis, and lower ROS and cytokine production, despite the persistent presence of viable JP2. Whilst in periodontally healthy neutrophils, JP2 binds to CD18 on cell surfaces, this is not the case in MIPP neutrophils, suggesting a potential role for CD18 in the periodontal susceptibility of MIPP patients

Self-reported influence of monetary grants in the choice of a medical residency in remote or under-served areas

Abstract Objectives To evaluate the effect of monetary grants on young physicians’ choice of remote or rural hospital-based practice. Background In late 2011, The Israeli Ministry of Health attempted to address a severe physician maldistribution, which involved severe shortages in remotely-located institutions (RLI). The policy intervention included offering monetary grants to residents who chose a residency program in a RLI. Methods A total of 222 residents from various disciplines were recruited; 114 residents from RLI and 108 residents from central-located institutions (CLI), who began their residency during 2012–2014. Participants were surveyed on demographic, academic and professional data, and on considerations in the choice of residency location. Results Residents in RLI attributed significantly more importance to the grant in their decision-making process than did residents from CLI. This effect remained significant in a multivariate model (OR 1.65, 95% CI 1.20–2.27, p = 0.002). The only parameter significantly associated with attributing importance to the grant was older age (OR 1.09, 95% CI 1.00–1.19, p = 0.049). Conclusion The choice of a RLI for residency may be influenced by monetary grants. This is consistent with real-life data showing an increase in medical staffing in these areas during the program’s duration. Further studies are needed to determine causality and physical practicality of such programs