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Background: We have previously discovered a subset of pathogenic-like T cells (CPL) that (1) possess inflammatory function; (2) has systemic migratory properties; (3) overlaps with synovial clonotypes; and (4) is correlating with active disease activity in rheumatoid arthritis (RA)1. The autoimmune antigenic targets of CPLs remain uncharacterised. Separately, we have demonstrated that mucosal tolerance re-education with the heat shock protein derived peptide, dnaJP1, has shown promising synergistic potentiation with hydroxycholorquine (P = 0.009 in ACR20 score) in a phase 2 trial with rheumatoid arthritic (RA) patients2. Consequently, whether CPLs reacts to the dnaJP1 peptide remains unknown. Objectives: Here we seek to investigate in a preliminary cohort of treatment naive RA patients, with the application of high parametric platform, mass cytometry, whether CPLs react to the dnaJP1 peptide. Methods: A cohort of adult RA patients (n=10 PBMC) and healthy controls (n=8 PBMC) were stimulated for 72hrs with dnaJP1 (10ug/ml). PBMCs were stained with a cocktail of metal conjugated antibodies and interrogated with mass cytometry (CyToF). The CyToF data is pre-processed with FlowJO and analysed with the EPIC analytics suite3. Results: We assessed the CD4 memory landscape in RA patients and healthy controls with mass cytometry. Unsupervised UMAP projections of total pooled CD4+ memory T cells reveal the presence of CPLs (CD4+HLADR+ T effectors). FlowSOM clustering revealed two clusters of CPLs expressing inflammatory cytokines (TNFa with IL-17A or IFNg) that are enriched in RA patients. Elevation of CPLs in RA patients as compared to controls were shown to be statistically significant (p + (p + (p + (p Conclusion: Overall, through the application of the high parametric technological platform, CyToF, we have demonstrated the enriched memory presence of a systemic population of inflammatory pathogenic T cells, CPLs. More importantly, CPLs elicited antigenic memory response in the presence of dnaJP1, unveiling a new mechanism through which aberrant self recognition could occur. This study identifies, CPLs, as an accessible pool of pathogenic-like T cells that could be used to advance our understanding of autoimmunity, and aid in designing diagnostic and therapeutic tools for RA. REFERENCES: 1 Spreafico R, et al. Ann Rheum Dis. 2016 Feb;75(2):459-65. 2 Koffeman EC, et al. Arthritis Rheum. 2009 Nov;60(11):3207-16. 3 Yeo JG, et al. Nat Biotechnol. 2020 Jun;38(6):679-684. Acknowledgements: NIL. Disclosure of Interests: None declared.
Leong et al. (Sat,) studied this question.