Immune cells in the blood are involved in both activating and suppressing inflammation and have important roles in autoimmune diseases such as MS.
Prof Trevor Kilpatrick and his team will determine if patterns of genes expressed by immune cells isolated from the blood can be used to predict the likelihood of ongoing disease activity and hence the subsequent development of MS in patients presenting with a first symptomatic demyelinating event.
Currently, the best predictor of the risk of developing MS in people with first demyelinating events (FDE) relies upon MRI evaluation. Molecular determinants of risk remain largely unexplored; however, the identification of accurate molecular predictors at FDE would complement MRI in identifying patients likely to benefit most from early aggressive treatment. In addition, the molecular profiles that are important in modulating risk of subsequent activity at disease onset could also provide clues to early immunological pathogenic events relevant to MS and its treatment.
People with established MS have been shown to benefit in the long-term from timely therapeutic intervention. A reliable test for the likelihood of ongoing disease activity amongst patients with an FDE would therefore be of great benefit. In particular, identification and validation of biomarkers able to predict the subsequent development of MS could translate into a rapid, inexpensive and non-invasive test to predict disease at the earliest possible stage. In addition, findings arising from this research that clarify the influence of immune cells at the earliest phase of disease could lead to new avenues of research and therapeutic approaches to treat MS.
Previous work carried out by Prof Kilpatrick and colleagues looked at the gene activity within particular immune cell types, the cytotoxic CD8+ T cells and the regulatory T cells. Cytotoxic CD8+ T cells are the white blood cells that kill abnormal cells, while the regulatory T cells are the immune cells that suppress the immune response and are thought to be functionally altered in MS. The preliminary study looked at the activity of all genes simultaneously in these cell types and showed differences in activity, but only examined a small number of patients. These results formed the basis of the current study, which will recruit a larger cohort of people with MS and will be utilising cutting edge techniques that have only recently become available.
Due to the nature of the study, people with MS and healthy controls must be recruited simultaneously and the blood samples obtained prior to the start of immunomodulating treatment. Nine patients have been recruited to the study and three different cell types purified from their blood at different time points. This includes two extra cell types over the original plan that will add extra value to the analyses and provide additional information on gene activity profiles of important immune cell types. The patients have been divided into two groups based on active or inactive disease. The recruitment of the FDE patients is ongoing and an additional patient cohort collected in the future will be combined with this dataset. The gene activity will be analysed using a technique called RNAseq which allows all gene activity across the genome to be analysed simultaneously.
In parallel, the team are profiling the amount of different types of immune cell across patients and controls. Analysis of this data shows no significant differences in the proportion of four different immune cell subsets, CD3+ T cells, CD8+ and CD8+CD56+ T cells, or Natural Killer (NK) cells either at presentation or at 3 months after presentation. No significant difference has been observed in the regulatory T cell population at either timepoint, but there was a trend towards a decrease in regulatory T cell proportion in FDE patients compared to healthy controls at 3 months post onset of symptoms.
The team continue to optimise methods to purify different types of blood cells from the blood samples and have optimised an assay to assess the activity of the beneficial regulatory T cells. We eagerly await the results of this study, since the findings will inform treatment decisions for people at the very beginning of their disease.
Updated: 13 June 2013
Updated: 06 January, 2011