In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis
Technical Report,10 Dec 2014,09 Dec 2018
Seattle Institute for Biomedical and Clinical Research Seattle United States
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The goal of this project was to test the hypothesis that cit-specific CD4 T cells present in rheumatoid arthritis RA patients exhibit a distinct cell surface phenotype and transcriptional signature that could be used to predict disease, response to therapy and identify novel therapeutic targets for the treatment of RA. Our studies resulted in novel findings, unique resources and new capabilities for the field of RA research. Our findings indicate that the dominant autoantigen driving disease may differ between individuals and that the character of the inflammatory response in RA may be linked to the antigen during the CD4 T cell response. Furthermore, we provide evidence that cit-antigen-specific phenotypes may stratify patients based on disease activity and disease duration. In addition, our whole blood RNA sequencing dataset suggest that T cell exhaustion is dysregulated in subjects carrying the HLA-DRB1 alleles associated with increased risk of RA. The project also generated in two unique cohorts of RA subjects that included Veterans a cross-sectional cohort and a longitudinal cohort with samples collected before and after initiation of therapy. There are banked samples with linked clinical data for each subject. Lastly, we also developed three new capabilities 1 a computational analysis tool for analyzing rare cell populations 2 a method for combining index sorting and single cell RNA sequencing of rare cell populations and 3 a panel of HLADRB10401 tetramers. We will share these resources and capabilities both within the RA community, and the field of autoimmune disease.
- Medicine and Medical Research