FROM BASIC SCIENCE TO THERAPEUTICS: THE STORY OF IL-2
- Abul K. Abbas, United States of America
REVERSING AUTOIMMUNITY COMBINATION OF RITUXIMAB & IVIG
- A. Razzaque Ahmed, United States of America
POLYAUTOIMMUNITY; WHAT IS IT AND WHY IS IT IMPORTANT?
- Juan-Manuel Anaya, Colombia
SPONDYLOARTHRITIS SPECTRUM OF DISORDERS: AUTOIMMUNE, AUTOINFLAMMATORY OR A BIT OF BOTH?
- Dennis McGonagle, United Kingdom
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.