OR.107. TIM-1 Plays a Crucial Role in the Expansion of Autopathogneic T-Cells and Regulation of Autoimmunity [abstract only]

T-cell immunoglobulin and mucin (TIM) family Members are differentially expressed on Th1 and Th2 cells. Polymorphisms of TIM-1 have been associated with susceptibility to asthma; however, its role in regulating autoimmunity has not been studied. Here, we have used an agonistic antiTIM-1 antibody (Ab, Clone 3B3) which has previously been shown to costimulate T-cell activation and expansion, to analyze the role of TIM-1 in the development and regulation of experimental autoimmune encephalomyelitis (EAE). Treatment with 3B3 dramatically enhances the severity of EAE as well as the frequency of encephalitogenic CD4+ T-cells and the production of IFN-g and IL-17 by these cells. Furthermore, administration of 3B3 breaks self-tolerance and induces EAE in the disease resistant B10.S strain. We have utilized another anti-TIM-1 Ab (RMT1-10) that does not costimulate T-cell activation in vitro. In contrast to 3B3, treatment with RMT1-10 inhibits the development of EAE and reduces the frequency of encephalitogenic CD4+ T-cells with a commensurate decrease in the production of IFN-g and IL-17. Treatment with RMT1-10 causes CD4+ T-cells to produce more IL-4 and IL-10. We provide evidence that both 3B3 and RMT1-10 bind to the same epitope in the Ig domain of TIM-1, but the binding affinity of 3B3 is much higher than that of RMT1-10. These data suggest that TIM-1 engagement with the agonistic Ab, along with TcR ligation, costimulates T-cell expansion with pro-inflammatory IFN-g and IL-17 production resulting in the breakdown of self-tolerance and development of autoimmunity, whereas blocking anti-TIM-1 Ab causes a decrease in the autopathogenic Th1/ThIL-17 responses. This study demonstrates that TIM-1 is a key cell surface molecule that regulates effector T-cell response and depending on hopw the molecule is engaged, autoimmune responses can be either enhanced or inhibited in vivo

Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specific for Tim-1 and identified two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specific T cells, the production of the proinflammatory cytokines IFN-γ and IL-17, and the severity of experimental autoimmune encephalomyelitis. In contrast, another anti–Tim-1 antibody inhibited the generation of antigen-specific T cells, production of IFN-γ and IL-17, and development of autoimmunity, and it caused a strong Th2 response. Both antibodies bound to closely related epitopes in the IgV domain of the Tim-1 molecule, but the activating antibody had an avidity for Tim-1 that was 17 times higher than the inhibitory antibody. Although both anti–Tim-1 antibodies induced CD3 capping, only the activating antibody caused strong cytoskeletal reorganization and motility. These data indicate that Tim-1 regulates T cell responses and that Tim-1 engagement can alter T cell function depending on the affinity/avidity with which it is engaged

Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients

International audienceNon-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis

Nutritional Profile and Dietary Patterns of Lebanese Non-Alcoholic Fatty Liver Disease Patients: A Case-Control Study

Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disease in the world. Dietary habits have a significant impact on the biological and physical profile of patients and increase the risk of NAFLD. The overall pattern of diet intake is more associated with health outcomes than nutrients. The aim of this study was to evaluate the nutritional profile and the dietary patterns of Lebanese NAFLD patients and compare it with controls. During this study; 112 NAFLD Lebanese adult patients (55 men and 57 women); and 110 controls (44 men and 66 women) were recruited. Dietary intake was evaluated by two 24-h recalls and a semi-quantitative 90-item food frequency questionnaire. Dietary patterns were determined by factor analysis. Results from the study demonstrated that 40% of cases belonged to the high fruit group as compared to 30% following a high meat; fast food dietary pattern. Both groups increased the odds of NAFLD by four-fold (p < 0.05). The traditional diet decreases the odds by 33% after adjustment with the covariables. The high fruit diet group was, as with the high meat, fast food dietary pattern, the main potential risk factor for NAFLD in Lebanese patients

Prospective Audit of Colonoscopy Practice in a Lebanese University Hospital

Background Colonoscopy has a great impact on diagnosis and management of the diseases of the colon. In general it's a safe and accurate procedure. No evaluation has been done of any endoscopic practices in a country where the practice of medicine is totally private. Objectives Prospective audit of technical success and complication rates of both therapeutic and diagnostic colonoscopy. Setting One endoscopy unit of a Lebanese university hospital. Patients and design 407 consecutive colonoscopies were evaluated over a 6-month period. Data were recorded for age and sex of the patients, indication of the colonoscopy, presence of comorbidities, patients risk stratification, administrated dose of anesthetic drugs. Data concerning the procedure itself were also monitored. Intervention Completion rate as well as complications reported during or post colonoscopy. All patients were called back by phone 48 hours and 1 month later to identify any related post-procedural complication. Results 407 patients underwent colonoscopy. All patients were sedated with midazolam, propofol and fentanyl. The overall caecal intubation rate was 99.99%. 70 snare polypectomies and 29 cold forceps excision were performed as well as 5 coagulations with Argon Plasma Coagulation. The most important post-procedural complication was chemical colitis in 2 cases. Limitations Patients and endoscopists satisfaction was not evaluated. It's an audit of a single tertiary French affiliated hospital. It does not necessarily reflect what's really happening on a national level. Conclusion This audit enabled us to change some of our practices; i.e. rinsing method of endoscopes. It stimulated the team to keep a high performance level without neglecting the risk of potential complications

Association between Periodontal Disease and Cognitive Impairment in Adults

IntroductionPeriodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults.Methods and materialsA systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure "oral disease" and outcome "dementia", "neuroinflammation" and "cognitive decline" were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies.ResultsThe results of included studies show that chronic periodontitis patients with at least eight years of exposure are at higher risk of developing cognitive decline and dementia. Oral health measures such as gingival inflammation, attachment loss, probing depth, bleeding on probing, and alveolar bone loss are associated with cognitive impairment. The reduction of epidermal growth factor (EGF), interleukin 8 (IL-8), interferon γ-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) in addition to over expression of interleukin 1-β (IL-1β) are significant in patients suffering from cognitive decline with pre-existing severe periodontitis.ConclusionsAll the included studies show evidence of an association between periodontitis and cognitive impairment or dementia and Alzheimer's disease pathology. Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear and warrant further investigation