Causes and Roles of Hypercitrullination in Preclinical Rheumatoid Arthritis

The goal of this project is to understand how the disease process of rheumatoid arthritis (RA) is initiated. Preliminary data suggest that blood cells obtained from healthy first-degree relatives (FDRs) of RA patients display abnormal features that are seen in untreated RA patients, indicating that those abnormal features predate the clinical symptoms of RA. The first aim of this project is to use biochemical approaches to characterize those abnormal features in blood cells from FDRs, and to establish a chronological and causal relationship among those features. The second aim is to use pharmacological and genetic approaches to examine how the cascade of the abnormal features is triggered. The final aim is to examine blood cells obtained from newly diagnosed RA patients before and after treatment to determine if effective RA treatment will mitigate these abnormal features. Taken together, this project will delineate a sequence of molecular events leading to the development of clinical RA symptoms and will bring us one step closer to the initial trigger of RA. Results coming from this project will contribute to early detection, prevention, and even cure of rheumatoid arthritis.