Dr Ben Crossett and Associate Professor Michael Barnett have received incubator grant support to pursue analysis using state-of-the-art techniques exploring the protein fragments that are displayed on the surface of cells in the body. The immune system recognises and responds to these fragments in order to generate an immune response to foreign molecules, or an autoimmune response. They are thought to play an important role in distinguishing ‘self’ and ‘non-self’ which breaks down in MS and also in neuromyelitis optica (NMO).
Around 70% of people with NMO have antibodies to a ‘self’ protein called aquaporin-4 (AQP4), this is a key distinguishing factor between NMO and MS. However, the remaining 30% have clinical signs of NMO but no AQP4 antibodies. It is not clear whether this group represents a variant of MS, a different subtype of NMO, or an entirely new disease entity.
Dr Crossett’s study will use specialised analysis techniques to compare groups of people with NMO (with or without AQP4 antibodies), and people with MS, to identify any differences in the type or amount of protein fragments that are displayed on cell surfaces. This will help to identify if the cell surface proteins could potentially be important in the failure of the immune system to identify ‘self’ and ‘non-self’ in MS and NMO disorders.
The findings of this study will not only help to increase our understanding of immune system function and how the immune system responds to protein fragments on cell surfaces, but will also help to develop a better understanding of the abnormalities in these autoimmune disorders and how they are defined. This knowledge can then form the basis for better diagnostic markers and potentially the development of novel, targeted therapies.
The goal of this project is to identify the protein which the immune system is attacking in the 30% of people with NMO who do not have AQP4 antibodies which attack the self. Dr Crossett and Associate Professor Barnett are using the state-of-the-art technique called mass spectrometry to answer this question. This technique involves isolating proteins that are on the surface of cells and then breaking these proteins into smaller chemical components and identify them using their mass. By calculating the mass of each of the components the researchers can identify each protein and therefore determine which protein the immune system is wrongly targeting in these people.
This group have been working on improving this highly sophisticated technique and have managed to increase the number of proteins that they can identify by over 10 fold. This advancement and other technical advancements have allowed the team to develop an entirely new method to comprehensively quantify the changes between the patients with and without AQP4 antibodies. This project, especially with their new detection ability, will give further insight into the differences between these groups and whether this represents a variant of MS, a different subtype of NMO, or an entirely new disease entity.
Updated: 12 August 2016
Updated: 03 January, 2014