I am a Clinical Research Associate and am interested in the effects of rheumatoid arthritis on skeletal muscle (read more about the RAMUS Study here). I am also training as a paediatric rheumatology doctor.
This was my first time attending a Therapeutic Tolerance Workshop, but I was well aware of the many internationally renowned speakers who were coming to Newcastle to share their expertise and research findings. I was particularly interested to think about how concepts of inducing immune tolerance could be applied to the children and young people that I see with rheumatic diseases.
The Workshop was jam-packed with content, and it was great to hear from clinicians and researchers from such a wide variety of backgrounds and disciplines. I was surprised to see the similarities in how research teams are utilising cell-based therapies in diverse situations including rheumatoid arthritis, multiple sclerosis, type 1 diabetes and organ transplantation.
I was only able to see one of the 'Great Debate' sessions (which discussed "Tolerance isn't tolerance without biomarkers"), but this format was a great opportunity to hear two experienced clinician scientists argue the importance of biomarkers in guiding tolerogenic therapies. The topic generated lots of heated discussion!
I hope to analyse muscle samples from patients with rheumatoid arthritis in the next year or so. This Workshop provided me with a great overview of current concepts of the immune dysregulation that occurs in RA which I am sure will prove very helpful in this regard.
In the next year we will have the results available for the Rheumatoid Arthritis and Muscle (RAMUS) Clinical Study, so I will enjoy looking through the data and reporting on our findings. To augment this research, I plan to perform gene expression analysis of paired skeletal muscle samples from the same group of patients.
I am an academic foundation doctor working under both the Translational and Clinical Research Institute at Newcastle University and the Newcastle upon Tyne Hospitals NHS Foundation Trust. I am now nearing the end of my first year of clinical training as a junior doctor and am due to apply for a specialty rheumatology training position in the near future. Prior to medicine, I graduated with a first-class honours degree in BSc Biomedical Sciences at Newcastle University and throughout this degree, including my dissertation project, I was always drawn to the immunology and chronic disease modules. I brought this interest forwards with me into medical school where I would seek out any and all opportunities to actively get involved with research, particularly rheumatology research to explore my interest further. I was fortunate in being signposted to Dr Faye Cooles, SpR in Rheumatology through mutual contacts, who kindly branched out and linked me to Professor John Isaacs, both of whom have now been my supervisors for the last five years which I am very grateful for. My current job role is split as 33% academic and 66% clinical time and I am currently in my academic block of the job. I have been exploring the role of neutrophils and its degradation products in early rheumatoid arthritis (RA) patient samples and linking this back to the interferon gene signature (IGS) work in early RA by Dr Faye Cooles as it is still unknown what may trigger a high IGS in predisposed individuals. Moreover, I am working on multiple smaller bioinformatic projects, case studies and reviews as well as lending my helping hands to colleagues for other laboratory work, which in turn has helped me revise and refine my laboratory skills after a six year hiatus from lab work altogether.
What were you looking forward to most about the workshop?
This fantastic four-day event was the fifth run of this workshop that has been held four-yearly since its establishment in 2005, with a one-year hiatus in 2021 secondary to the COVID-19 pandemic. The event brought together experts in therapeutic tolerance from across the globe and was the perfect platform to network, initiate collaboration and learn from expertise. This year, the event was held at The Catalyst, Newcastle University, led by Professor John Isaacs and was supported by the Newcastle Biomedical Research Centre and Newcastle Health Innovation Partners.
What were your impressions of the conference?
The event was extremely jam packed full of talks, discussions, and debates, split into a total of 13 sessions delivered over the course of four days. The format of this therefore meant there were around 5-7 talks per session with a grouped Q&A section following each session. Many of the speakers did a fantastic job of delivering their talks within a short space of time and in doing so, getting their points across succinctly and effectively. The organisers also did a great job at including and involving speakers who unfortunately could not make the event in person and therefore were able to deliver their talks over Zoom and join in on the Q&A sessions in the same respect. The event was run extremely smoothly and was considered overall a huge success across the board.
The first day’s sessions were themed “regulatory cells in tolerance induction” and “biomarkers and immune monitoring”, which consisted of a number of talks, highlighting to us which cell types have predominantly been found to play a role in autoimmunity and which could act as potential biomarkers in detecting disease at an early stage and aid in prognostication.
The next morning was an early 8am kick-off with a keynote talk on “Developing therapies to target immune regulation” from Professor Shimon Sakaguchi, founder of Tregs and their role within the immune system. This was shortly followed by three further sessions throughout the day on “Human tolerance trials – the story so far”, “delivering therapies to patients” and “co-stimulation blockade”. As a clinician, I thoroughly enjoyed this day of the workshop and probably the most, because it really showcased the current translational bench to bedside science that is occurring around the world and the impact it is having on patients and healthcare systems.
The third day again started with an 8am keynote talk from Sir Robert Lechler on immunosuppression therapy and allografts, which was followed by a further three sessions on “antigen specific tolerance induction”, “miscellaneous aspects of tolerance induction” and “antigen agnostic tolerance and its breakdown”. Again, despite my limited understanding in basic sciences, I found the content fascinating as it was based heavily on patient benefit and impact and how these novel therapies were changing lives. I was particularly surprised but fascinated to hear about how CAR-T cells were being used to treat systemic lupus erythematosus (SLE) as it is prevalent in oncology but is yet to be established in the rheumatology field.
The final day ended with talks on “cellular therapies” and “drug-free remission”. These were perfect topics to end the workshop as it really made us all consider what the other end of the spectrum looked like. I.e., as a patient, nobody wants to stay on medication forever so what biomarkers can we use to determine those who don’t actually need to? The final talk was delivered by our host, Professor John Isaacs to really stimulate thoughts, discussions and viewpoints on remembering to consider the whole picture, i.e., in the case of rheumatoid, to consider the stroma, and not just what is within it which could lead us to further answers.
What were the highlights?
I was awe to learn that I was in the presence of some of the fathers of immunology at this event, with Professor Tak Mak, founder of the T cell receptor and Professor Shimon Sakaguchi, founder of Tregs, delivering captivating and stimulating talks themselves. It was an honour to speak to them both in an informal setting and hear their stories of discovery. I also enjoyed “The Great Debates” section of the workshop with two debates over the middle two days.
The first was on the topic “This house believes that tolerance isn’t tolerance without biomarkers” which had Professor Ranjeny Thomas arguing for the motion and Sir Robert Lechler arguing against. I had never experienced a live debate before like this, especially in the context of immunology. and it was exciting to watch as each side had to defend their viewpoint from each other as well as from the audience who would ask thought provoking questions to potentially counteract their arguments.
The second debate was based on the topic “This house believes that T-cells are the undisputed therapeutic tolerance target” with Dr Michael Maldonado arguing for the motion and Professor Claudia Mauri arguing against (why B cells are the ideal target). Again, this similarly led to a stimulating debate between both parties and the audience and was definitely one of the highlights of the event.
How will the event help you in your work going forward?
Initially, my plan to attend the event was predominantly to hear talks and discussions from experts around the world. However, by immersing myself within the environment, discussions, and people, I found the event extremely motivating in planning my next steps and career moves.
There were many interesting talks both from invited speakers and oral presenters that shared research findings and knowledge relevant to my current research projects as well as potential areas that I would like to explore further such as the role of Tregs in refractory arthritis and the interferon gene signature’s role in checkpoint induced inflammation. It was also useful to hear about what other people, laboratories and teams are currently working on and their objectives and end goals.
What are your planned next steps in your work?
I had not previously thought about potentially doing my PhD abroad nor applying for a fellowship prior to this event. However, following discussions and networking with experts from Australia, Canada, United States of America, Berlin and the Netherlands to name a few, has really changed my mind about this and has motivated me to start researching options outside of the UK and what elements in my CV I would need to build upon to attain one of these positions.
Furthermore, it has made me think about where to attain funding from as well as delve into further reading to find and confirm a research project that I would like to explore further within my PhD.