The expression of toll-like receptors in B-chronic lymphocytic leukaemia

• Main Author: Oakes, N.
• Published: University of the West of England, Bristol 2015
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767150

Chronic Lymphocytic Leukaemia (CLL) is the most common form of Leukaemia in the Western world and has a highly variable clinical course. Continuing advances in the range of therapeutic options available to clinicians require reliable prognostic indicators that can be used to group patients accurately according to their risk of disease progression, thereby allowing meaningful comparisons of treatments. The expression of Toll-Like Receptors (TLR) on cells involved with the disease process in CLL was studied to establish links between levels of expression and the disease process. The expression levels of 5 different TLR were measured on a variety of haemic cells and compared with the TLR expression levels seen on their normal counterparts. Flow cytometric analysis was used to establish the expression levels of TLR 1,2,3,4, and 9 on peripheral blood Monocytes, T Lymphocytes and B Lymphocytes from 129 patients. These results were compared with the TLR expression on corresponding cells from an equal number of age and sex matched controls. Further studies were performed which established the detrimental effect that storage of samples has on TLR expression, and also to compare TLR expression in patients who exhibited a positive Direct Antiglobulin Test (DAGT), with those that were negative for the DAGT. Results from the study show that both T and B lymphocytes from CLL patients showed statistically significantly different levels of TLR expression when compared with lymphocytes from age and sex matched controls. TLR expression levels on monocytes were similar in both patient and control groups. When comparing TLR expression between patients who were DAGT positive and those that were negative, a statistically significant difference was found in TLR9 expression on T lymphocytes. These findings have established that that there are statistically significant differences in TLR expression on lymphocytes when comparing CLL patients with age and sex matched controls. It also establishes the differences in TLR expression levels seen in DAGT positive and DAGT negative patients. From findings made during this study, it is hypothesised that there may be a link between differential TLR expression and the autoimmune disease frequently reported in CLL.