Nirdhvaitha Thinniyam Sakthi Kumar
Research Mentor: Chetna Soni
Mentor Department: Internal Medicine, Medicine
Author(s): Nirdhvaitha Kumar, Chetna Soni
Session: Session 6 (3:00 PM – 3:50 PM)
Presentation Type: Poster 72
Abstract
DEK is a proinflammatory protein secreted from macrophages during inflammation. DEK promotes arthritis, specifically, Juvenile Idiopathic Arthritis by promoting neutrophil activation and chemotaxis: the directed movement of immune cells into tissues, like joints. Therefore, blocking DEK with anti-DEK monoclonal antibodies can reduce inflammation in autoimmune conditions such as arthritis. Our study uses monoclonal antibodies against human and mouse DEK to block DEK in mice that have induced arthritis. We will then induce arthritis in the mice and see if the anti-DEK antibodies reduce arthritis-related inflammation compared to mice that are treated with a random monoclonal antibody. My specific experiments in this project will include testing the serum concentration of anti-DEK antibodies in circulation. Two different antibodies will be tested. We will use two models of arthritis: (1) the zymosan-induced arthritis model, and (2) the collagen- induced arthritis model. Mice will be injected with anti-DEK antibodies at a dose of 25 mg/kg. In the zymosan-induced arthritis model, the mice will be injected once, and serum will be collected on day-2 and day-7 after arthritis induction. In the collagen-induced arthritis model, the mice will be injected with the anti-DEK antibodies every fourteen days for a total of 42 days. Serum will be collected on days 14, 28 and 42, and antibody concentration will be determined through Enzyme-Linked Immunosorbent Assay (ELISA). These experiments will determine the optimum dosing of anti-DEK antibodies required to suppress inflammation and arthritis in mice. This project will help in the preclinical validation of therapeutic antibodies that block NETosis in vivo and could be useful in treatments of RA and other NETosis-driven inflammatory diseases.
