Tu111 - Circulating Pathogenic Like Lymphocytes Are Mechanistic Targets for the Induction of Immune Tolerance in Rheumatoid Arthritis

Ahmad Mohamed Lajam – Translational Immunology Institute – Singhealth/Duke-NUS Academic Medical Centre; Chin Teck Ng – Department of Rheumatology and Immunology – Singapore General Hospital; Salvatore Albani – Translational Immunology Institute – Singhealth/Duke-NUS Academic Medical Centre

Abstract Text: In published work, using a high dimensionality approach, we identified a subset of pathogenic-like T cells (CPL) that (1) has a strong inflammatory function; (2) is able to recirculate through the sites of autoimmune reaction; (3) is highly enriched in synovial clonotypes; and (4) is correlating with disease activity rheumatoid arthritis (RA). The antigenic targets of CPL are still unknown. We have also previously identified a heat shock protein derived peptide (dnaJP1) as a dominant T cell antigen in RA and developed a tolerance-induction clinical trial program showing promising clinical efficacy in Phase IIa. Here, we investigated whether dnaJP1 peptide could have any effects on CD4+HLADR+ T cells. We stimulated with dnaJP1 PBMCs from a cohort of treatment naive RA patients and healthy controls, and assessed the CD4 memory landscape using our EPIC AI-powered Cytof platform, We found significantly elevated in RA patients two clusters of CPL effectors expressing TNFa with IL17A or IFNg, and proliferating in the presence of the dnaJP1. In summary, our data identifies in dnaJP1-specific CPL a mechanistic target of clinical relevant immune toleration. It also identifies CPL as an easily accessible pool of pathogenic-like cells, which may be used to advance our understanding of aberrant self-recognition, as well as to design targeted diagnostic and therapeutic tools.