Profiling patients with type 2 diabetes on the paradox idea: the underappreciated role of toll-like receptors in B lymphocyte activity
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Abstract
Type 2 diabetes (T2D) is a growing concern in most developed countries and in the US. The disease is associated with increased risk for certain diseases such as cardiovascular disease, kidney disease, retinopathy, neuropathies, dementia and most types of cancers. Many studies have established an association between chronic inflammation and diabetes pathology. Part of the pathology of T2D involves a chronic state of inflammation in which the immune response is altered. Toll-like receptors (TLRs), specifically Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4), play critical roles in mediating inflammation. Past studies have looked at the role TLRs play, but have not characterized their combined effects or the influences of other covariates such as various clinical and immunological parameters. This study aimed to investigate the role of TLRs, specifically TLR2 and TLR4, in B lymphocytes and how this expression can be used to profile and characterize disease severity in patients with T2D. This study used a subset of patients (n=SO) enrolled in an IRB approved and industry sponsored study in the Ganley-Leal lab in the Section of Infectious Disease Laboratory at Boston University Department of Medicine. Patient data was obtained from medical records, a short questionnaire, and heparinized blood samples. Serum concentrations of High Mobility Group Protein 1 (Hmgbl) and Limulus Amebocyte Lysate (endotoxin) were measured along with B lymphocyte TLR expression and cellular responses to TLR ligands. Bivariate tests, tests for linear associations and an analysis of variance (ANOVA) were performed on clinical, immunologic and disease severity index parameters. The study found that TLR2 expression on B cells was both significantly associated and correlated positively with triglyceride levels. High basal IL-8 production was important in characterizing level of response for clinical parameters. The data suggests that IL-8 production and DSI score, in conjunction with TLR2 expression by B cells, can help profile patients with T2D and characterize additional risks that may be overlooked when using parameters like glycated hemoglobin. Further research is needed to explore the role of B cells and TLR activity in chronic inflammatory processes and in patients with chronic inflammatory diseases such as T2D.
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Thesis (M.A.)--Boston University
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