Tu167 - Dr. Jeykyll and Mr. Hyde- the Curious Case of the Mixed and Overlap Disease in Rheumatology; Immunological Perspective

Abstract Text: Immunogenetics plays a vital role in the expression of rheumatologic diseases. The HLA is the critical link between the putative auto-antigen, the subsequent T-cell cytotoxicity, and the B-cell autoantibody formation. This is reflected in the clustering of patients into “B” and “DR” groups of inflammatory disorders—the spondyloarthritis group with the HLA-B27 allele, the rheumatoid arthritis group with the HLA-DRB-01,04, etc. However, immune-response genes like the PTPN22, ERAP, and other genes associated with cellular and molecular machinery of the immune response can be the more important “final common pathways” associated with immune pathology.
Part 1 of the talk will discuss the findings from the cohort at our center and describe the” overlap musculoskeletal disorder”- patients with contrasting forms of inflammation in single patients, or their clustering in first-degree relatives. This relates to the diagnosis of rheumatoid arthritis which is a prototypical autoimmune inflammatory disorder and spondyloarthritis which is an autoinflammatory inflammatory disorder. The possible heritable immune and cellular/molecular mechanisms for this unique scenario will be discussed through illustrative case summaries and treatment effects. The related phenomenon of “unmasking” phenotypic traits when patients are treated with targeted therapies and how this relates to “overlap disorders” will be part 2 of my talk. Illustrative case scenarios from my psoriatic arthritis cohort and the research agenda arising from this will be added to the discussion will be discussed.