IAB Honorary member – Past President: Angela Vincent

6 December 2021
200 Views

?…what was Neuroimmunology like when you started your career… 
Neuroimmunology didn’t exist in the 1970s when I started to be involved with the acetylcholine receptors and antibodies to them. My experience at that stage was with the nervous system and actually I have never really learnt that much basic immunology other than what I have needed to pursue antibody-mediated disorders.  In fact, despite decades of work on multiple sclerosis,  Neuroimmunology didn’t really get started as an independent field until 1982 (first international conference on Neuroimmunology) and 1988 when a small international group met including Cedric Raine who subsequently became a founding editor of JNI.

?…what have the transformative technical changes been…
Because our work has been almost entirely on antigen-specific antibodies in muscle and brain disorders, the most important developments have been in molecular neuroscience rather than immunology!  Particularly in being able to identify (initially often using radioactive toxins) clone and express different membrane proteins as targets for antibodies in autoimmune forms of neuromuscular junction and, latterly, CNS disorders such as autoimmune encephalitis.  We have always been lucky to have good molecular biologists in the group particularly David Beeson.  Of course, the availability of fluorescence labelling of commercial antibodies has been essential for many of the studies we have done, the underlying studies have been molecular.

?… what discovery has surprised you most….
When we first realised that a patient with severe cognitive changes, psychiatric features, severe sleep disorders and antibodies that immunoprecipitated voltage-gated potassium channels (VGKC), improved considerably following plasma exchange and steroids, I was not entirely surprised, as our work had been moving in that direction; but I was certainly very excited although also cautious –in fact, I insisted that we were careful not to over-interpret the role of the VGKC antibodies in the CNS symptoms but also considered systemic dysregulation of neuropeptides as a possible cause of his condition.  Now we know that this patient had very high titres of antibodies to a VGKC-associated protein, CASPR2 (that is complexed within the VGKC complex), and that those antibodies are pathogenic in mouse models.  Another pleasant surprise was probably when we first showed that pregnant mice can transfer human antibodies to their foetuses; the experts I had spoken to said it would not happen, but they were wrong and we have now used that model in a number of novel studies.   Overall, however, my experience is that even if you are excited or surprised by a finding, that doesn’t last long as you realise how much work needs to be done to confirm your initial finding and establish its relevance.

?… what are your expectations for the future…
There are a few aspects of our work that I would like to see developed further – particularly the role of maternal antibodies in causing neurodevelopmental disorders.  I would like to see much more global cheap bed-side type testing for autoantibodies to surface neuronal, nerve and muscle antigens; that would mean that these relative rare conditions could be identified and the patients treated.  I would like to see a range of non-immunological drug treatments trialled that might modify the pathogenic mechanisms to achieve results within hours to days, while the immunotherapies begin to work.

 

?… where do you think the field is getting to…
I am concerned that there is too much expectation that the immune system is involved in neurodegenerative disorders and that further work in this field will lead to novel and successful therapies.  I do believe that the immune system can play a role and that genetic or environmental factors affecting the immune system as well as those that affect the nervous system might explain many aspects of these diseases, but whether further knowledge in this area will lead to successful new treatments is to me, at least, not so clear.  I hope I am proved wrong.  With respect to the antibody-mediated CNS syndromes, there is still a lot of imaginative and detailed work to be done to identify where and how each antibody causes the, often myriad, symptoms.

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