Prof Dennis McGonagle to deliver annual Institute of Medicine Stearne Lecture

Professor Dennis McGonagle, Deputy Director at the NIHR-funded Academic Unit for Musculoskeletal Diseases and Leeds Teaching Hospitals NHS Trust, will deliver the Stearne Lecture at No 6 Kildare Street on Thursday, 30 November 2023.

Titled, This drug might help you, but it will definitely help me!, his lecture will draw on his foundational studies into tissue microanatomy and seronegative arthritis localisation to sites of high physical stress resulting in the modern classification of Immune Mediated Disease published in PLoS Medicine in 2006 -  A proposed classification of the immunological diseases.  The study, which outlined that inflammation against self was not always autoimmune but that tissue-specific dysregulation of innate immune mechanisms (or autoinflammatory mechanisms) defined a new immunotherapeutic boundary of self-directed inflation.  This provides immune cartography for inflammatory disease therapy.

“Dealing with disease localisation in inflammation in arthritis, we noted on Magnetic Resonance Imaging in early arthritis that some diseases attacked the joint lining (synovium-in rheumatoid arthritis) whilst others attacked sites where ligaments anchored to the bone (psoriatic arthritis and ankylosing spondylitis). Linking this to immunogenetics and immunology, we realised there were two major types of inflammation against self, and not all are autoimmune”.

“As physicians, when presented with a patient we need to determine if the disease pathology is based on something going wrong in the primary and secondary lymphoid organs (that make T and B-cells) or whether something is wrong in the tissues themselves that triggers activation of an otherwise normal B and T-cells immune system.  The latter scenarios may arise in inflammatory bowel disease where tissue-specific sensing of bacteria in the gut or abnormal responses to physical stress in ligament attachments in ankylosing spondylitis triggers disease” Prof McGonagle explains.

“In reality, an immunological disease continuum exists and an interaction between autoimmune and innate immune mechanisms determines pathology.  Crucially, it transpires that diseases that are exclusively innate immune mediated or intermediates between innate and adaptive immunity are very responsive to IL-1 blockade or IL-23 and IL-17 blockade and other drugs such as colchicine - the latter of which was discovered by the Ancient Egyptians.”  The mouse and human immune systems may be very different and a way of discerning the immunopathogenesis of human disease is vital.  

“The title of my Stearne Lecture reflects the fact that medicine is an art as well as a science and patients may lack clearly defined phenotypes and we empirically chose a treatment strategy to cover the best fit clinical scenario.  Quite often the strategy works so therapy also serves as a diagnostic test, but sometimes it does not work.  If patients do not get better but we can move on with a better understanding of the disease we are treating – we switch our strategy and target another part of the immune system- hence the physician but not the patient benefits from the initial therapy strategy.” Described by Professor Anthony O’Regan, Dean of the Institute of Medicine, as a paradigm shifter, Prof McGonagle has forged a career on answering the unexplored in rheumatology. In 1998, he first raised the idea that there are two different types of inflammation of the joints. Now when joints are scanned, two patterns of disease are evaluated to help to determine treatment strategies. Prof McGonagle continues to push boundaries and shape how we practice medicine for the patient of the future.

Hear more from Professor McGonagle at the Stearne Lecture, hosted by the Institute of Medicine at the Royal College of Physicians of Ireland on Thursday, 30 November at No 6 Kildare St.  Book here.