In-Depth Analysis of Citrulline-Specific CD4 T Cells in Rheumatoid Arthritis
Abstract
Rheumatoid arthritis (RA) affects over 1.3 million Americans. It is a chronic disease that if untreated results in pain and permanent disability. Our current approaches to treatment are expensive, lead to systemic immune suppression, and do not cure the disease. It is now known that joint-associated proteins are biochemically altered by inflammation and that these alterations provoke cellular immune responses against joint tissues. In particular, T cell responses directed against the joints drive the development of RA, but are not well understood. Our research group has developed the ability to identify and isolate joint- specific T cells from the blood of patients with RA using a tool called HLA (human leukocyte antigen) class II tetramers. In this proposal, our objective is to utilize this tool to better understand the unique features of joint-specific T cells and how these features change with disease activity and with therapy. This information will be useful to diagnose RA earlier, which could allow for earlier intervention, decreasing the morbidity of the disease. Further, it may be a means to predict response to therapy very soon after the initiation of a new therapy, which would decrease the expense and exposure to drugs that are unhelpful or potentially harmful. Most importantly, we will use the tetramers to isolate the joint-specific T cells from patients, and we will examine these cells using a new technology that will allow us to sequence the expressed genes in each cell, with the goal of determining how better to target those cells therapeutically. This will allow us to determine the unique features of the cells that cause disease in RA. This work will study a broad swath of individuals with RA who are currently receiving "standard care" through the rheumatology clinic in Seattle and from the Department of Veterans Affairs rheumatology division, making the findings from this study relevant to the majority of RA patients. The findings from this study will not only enhance our scientific knowledge related to the causes of RA, but also identify new determinants that can be therapeutically targeted while protecting the remaining immune cells needed for the patients health.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510004
Entities
People
- Bernard Ng
Organizations
- Seattle Institute for Biomedical and Clinical Research
- United States Army