In-Depth Analysis of Citrulline-Specific CD4 T-Cells in Rheumatoid Arthritis

Abstract

The goal of this project is to test the hypothesis that cit-specific CD4 T cells present in rheumatoid arthritis (RA) patients exhibit a distinct cell surface phenotype andtranscriptional signature that could be used to predict disease, response to therapy and identify novel therapeutic targets for the treatment of RA. In Year 3, we havecontinued to make significant progress for all our goals. For Aim 1, our findings suggest 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, the dominant autoantigen driving disease ultimately may determine the response to therapy. For Aim 2, our analysis of the 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. A twelve-month no-cost extension was recently approved to allow us to do additional bioinformatics analysis to strengthen these results for publication. The no-cost extension was also approved for additional time to complete both the RNA sequencing of antigen-specific T cells in Aim 2 and the ex vivo tetramer analysis of the samples from the longitudinal cohort in Aim 3.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2018
Accession Number
AD1050556

Entities

People

  • Bernard Ng
  • Jane H Buckner

Organizations

  • Seattle Institute for Biomedical and Clinical Research

Tags

DTIC Thesaurus Topics

  • Antigens
  • Arthritis
  • Autoimmune Diseases
  • Biological Therapy
  • Blood
  • Cells
  • Computational Biology
  • Data Analysis
  • Department Of Veterans Affairs
  • Dermatologic Agents
  • Disease Attributes
  • Genetics
  • Health Care
  • Health Services
  • Lymphocytes
  • Medical Personnel
  • Rna Sequence Analysis

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology
  • Immunology and Pathology
  • Psychological Intervention/Treatment for Stress, Anxiety, PTSD, and Related Emotional and Cognitive Health Symptoms.