Key words: autoimmunity, antigen-processing, rheumatoid arthritis, autoantibodies, T cells.
The major focus of my laboratory is to identify mechanisms that drive the development and propagation of autoimmune diseases, with an emphasis on biomarker discovery and translational application. Using biospecimens from patients with autoimmune diseases, we have gained valuable insights into the role of post-translational modifications in generating neo-epitopes capable of stimulating autoreactive T cells and the role of autoantibodies in amplifying disease. Much of our work has focused on the biochemical and immunologic properties of the calcium-dependant peptidyl arginine deiminase (PAD) enzymes, key pathogenic enzymes in rheumatoid arthritis (RA) that are targeted by both B and T cells. We have discovered a novel group of human anti-PAD4 antibodies that activate the PAD4 enzyme by lowering the amount of calcium necessary for catalysis and have shown that proteolysis of PAD4 by the serine protease granzyme B results in altered antigen processing and presentation of peptides capable of stimulating autoreactive T cells from patients with RA. Currently, we are exploring the link between genetic and environmental factors in the generation of anti-PAD4 antibodies, studying the effect of post-translational modifications on antigen processing and presentation, and harnessing high-throughput techniques to study the gender bias of autoimmune diseases.
Lab website: https://www.darrahlab.org
Publications and Interests: https://jhu.pure.elsevier.com/en/persons/erika-darrah