Dennis McGonagle, United Kingdom
Moderator of 1 Session
Presenter of 2 Presentations
SPONDYLOARTHRITIS SPECTRUM OF DISORDERS: AUTOIMMUNE, AUTOINFLAMMATORY OR A BIT OF BOTH?
Abstract
Background and Aims
Spondyloarthritis (SpA) represents a spectrum of inflammatory disorders that comprises related but phenotypically distinct inflammatory diseases including psoriatic arthritis (PsA), non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (ankylosing spondylitis (AS)), arthritis associated with inflammatory bowel disease (IBD) reactive arthritis, juvenile idiopathic arthritis and acute anterior uveitis related arthritis.
Methods
Perspective
Results
These diseases were originally viewed as autoimmune, but now, are known to have a strong innate immune or autoinflammatory initiation phase characterized by disease localization to tissue-specific sites based on the nuances and microanatomy and immunology of these sites. Experimental models show that dysregulation of pivotal pro-inflammatory cytokines including TNF and IL23/17 axis can drive an inflammatory state. Several monogenic forms of SpA have been reported including DITRA and DIRA which appear to due to innate dysregulation of the IL-36 and IL-1 pathways. However, certain autoantibodies have been described including p-ANCA in IBD related arthritis and recently anti-CD74 antibodies in axial spondyloarthritis. These are likely to be secondary to tissue damage, rather than primary drivers. Unlike the somewhat contentious humoral autoimmunity in SpA spectrum disorders there is more compelling evidence for CD8+ T-cell driven immune responses in the SpA spectrum disorders and given the MHC class I associations (HLA-B27 in AS and uveitis, HLA-Cw06 in skin and HLA-B51 in BD), collectively these conditions have been termed “MHC-I-opathies.”
Conclusions
The SpA group of disorders share different aspects including genetic predisposition, pathophysiology and management and they are immunologically heterogeneous but overall interaction between innate immunity and CD8+ T-cells forms a broad overarching basis for disease.
MECHANISTIC CLASSIFICATION OF IMMUNE CHECKPOINT INHIBITOR TOXICITY AS A POINTER TO MINIMAL TREATMENT STRATEGIES TO FURTHER IMPROVE SURVIVAL
Abstract
Background and Aims
Improved anti-tumour responses under immune checkpoint inhibition (ICI) are associated with concomitant autoimmune disease development termed immune-related adverse events (irAEs), of which approximately 5% are rheumatic in nature. We have reviewed the literature to assess whether immunosuppression therapy of irAEs may negatively affect the patient's outcome.
Methods
Review of the literature
Results
Oncologists and other specialists vigorously treat irAEs in spite of the generally accepted beneficial effect of irAEs on tumour survival. Herein, we highlight mechanistic insights on how tumour responses and certain types of autoimmunity appear to be inextricably linked around CD8+ T-cell mediated responses and those strategies that interfere with such shared immunopathogenesis could impact survival. We discuss the possible circumstances in which intensive immunosuppressive therapy for irAEs that occur with ICIs might blunt anti-tumour immunity. We also discuss potential therapeutic strategies for emergent ICI related autoimmunity and propose some treatment considerations and research questions to minimize the impact of overzealous immunosuppression strategies on tumour responses. Thus, refraining from using powerful therapeutic armamentarium to treat irAEs, especially when these are not considered as life-threating might improve the prognosis of ICI therapy.
Conclusions
Permitting the controlled “fire burning” of an activated immune response to ultimately stall cancer progression and further improve long-term survival is a strategy, which merits consideration. Adopting the view that survival is better in cases with irAEs who receive corticosteroids compared to subjects who do not develop irAEs is potentially ignoring the further improved survival attainable by letting the immune fire continues to burn.