Screening for Autoantibody-Producing Cells
Abstract
Lupus is a devastating autoimmune disease characterized by inappropriate immune responses. There is currently no cure for lupus and available treatments suppress normal healthy immune responses. Although these treatments relieve some symptoms of the disease, they also result in impaired responses to infections without curing the disease. Antibodies are molecules made by white blood cells called B lymphocytes to help fight infectious agents. An underlying cause of lupus is over-production of a subset of antibodies that recognize an individual’s own tissues, called autoantibodies. Some treatments for lupus target all B lymphocytes, eliminating autoantibody-producing cells, but they also leave individuals unable to produce antibodies against infectious agents. It is currently not possible to distinguish the B lymphocytes that make autoantibodies from the B lymphocytes that are needed for healthy immune responses. Exposure to the common virus Epstein Barr Virus (EBV) and other environmental triggers are thought to activate B cells and initiate autoantibody production in patients with lupus by unknown mechanisms. In this study, we will determine if the new biomarkers we have developed will specifically identify the activated B cells that are precursors of the cells which will eventually produce autoantibodies. We will use patient blood cells on consecutive visits to determine if increases in this activated B cell type occur before increases in autoantibodies are detectable in a patient’s blood. In addition, we will isolate these cells and determine if they produce the same types of autoantibodies that are produced in that patient’s blood at the next visit. Our objective is to determine if we can identify precursors of autoantibody-producing cells in individual patients before patients produce autoantibodies. If our studies are successful, patients could be screened using a simple blood test, with no additional risk, to detect increased numbers of these cells before they mature into autoantibody-producing cells. The ability to diagnose upcoming increases in disease activity before they occur could positively impact individual patients’ quality of life by allowing personalized alterations of therapies by their physicians. This should be particularly helpful for patients who undergo disease flares with increased autoantibody production. If successful as a screening tool, this outcome could lead to the availability of prescreening tests within 5 years. More importantly, if we can selectively identify the activated B cells that will eventually develop into autoantibody-producing cells, we should be able to develop methods to specifically target this subset of B cells, leaving other healthy B cell subsets intact. This is a long-term goal that would require clinical trials and take approximately 10 years. However, the potential impact of such a treatment is high. The proposed studies lay the groundwork for testing these long-term goals.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310271
Entities
People
- Carol Webb
Organizations
- United States Army
- University of Oklahoma Health Sciences Center