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UK funding (£214,841): MICA: Investigating the pathogenic role of T follicular helper cells and their therapeutic targeting in primary Sjogren's syndrome Ukri1 Sept 2015 UK Research and Innovation, United Kingdom
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MICA: Investigating the pathogenic role of T follicular helper cells and their therapeutic targeting in primary Sjogren's syndrome
| Abstract | Sjögren's syndrome (SS) is the second most common rheumatic autoimmune disease with a prevalence affecting between 100,000-250,000 in UK and a predominance in women (female to male ratio is 9:1). SS is characterised by immune cell infiltration in the salivary and lacrimal glands leading to dry mouth and dry eyes. However, SS is a highly heterogeneous disease with 30/40% of SS patients developing moderate to severe extraglandular manifestations and 5% developing a form of cancer (lymphoma) which arise from B cells, a type of white blood cells. Currently, the treatment of SS is unsatisfactory with no effective therapies available. Studies from our and other groups have identified a subset (30-40%%) of SS patients which present B cell clusters in the salivary glands called germinal centres. These patients have a more active disease and have a 16-fold higher risk of developing lymphoma than the remaining patients without germinal centres. Previous work has demonstrated that another subset of very specialised white blood cells, called T follicular helper (Tfh) cell, play a critical role in supporting the survival and activation of B cell in germinal centres. While the role of Tfh is well established in germinal centres which arise in lymphoid organs (i.e. the spleen, tonsils or lymph glands) their role in aberrant germinal centres which form during chronic inflammatory disease is unknown. Thus, in this application, which is a Partnership between 3 UK Universities and MedImmune, a pharmaceutical company, we aim 1) to investigate the role of Tfh in promoting the disease in a series of studies involving human samples and animal models; 2) to address whether blocking Tfh in preclinical studies with novel pharmaceutical compounds will impact on various features of the disease, such as the activation of B cell in the salivary glands and the amelioration of salivary flow and 3) to identify key factors which will allow us to understand which SS patients are more likely to respond to novel treatment targeting Tfh in SS. This proposal have the objective to have immediate clinical impact as MedImmune and the Academic partners of this application are working closely together to bring novel treatments in the clinic for the benefit of patients with SS (pilot clinical studies planned for late 2015 and in 2016 in UK). It is envisaged that, if successful, this work will also impact on other medical conditions which might benefit from targeting Tfh cells. Specifically, we anticipate that this proposal will bring new knowledge and will identify key factors which will allow us to measure the level of activation of Tfh in different patients. This work will be essential because will inform on which SS patients are more likely to respond to the new treatments that we are developing and will be tested in upcoming clinical trials in SS. These trials will be based on the concept of "target validation", whereby the work done in this project will put us in the position to stratify patients based on the level of Tfh present in their salivary glands (or in their blood). We hope that this approach on one side will increase the response rate and on the other side will prevent SS patients who are unlikely to respond from being exposed to the potential side effects of the novel treatments. |
| Category | Research Grant |
| Reference | MR/N003063/1 |
| Status | Closed |
| Funded period start | 01/09/2015 |
| Funded period end | 31/08/2018 |
| Funded value | £214,841.00 |
| Source | https://gtr.ukri.org/projects?ref=MR%2FN003063%2F1 |
Participating Organisations
| Queen Mary University of London | |
| Stanford University | |
| CARDIFF UNIVERSITY | |
| Servier Laboratories | |
| UNIVERSITY OF CAMBRIDGE | |
| University of Paris | |
| University Medical Center Gronigen | |
| MedImmune (International) |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: Queen Mary University of London, London.
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