Miriam Shelef, MD, PhD, assistant professor, Rheumatology, has been awarded $400,000 over two years as an FY2019 Innovative Research Award from the Rheumatology Research Foundation.

The study funded by this award will build on previous research by Dr. Shelef and her team, which identified a protein called peptidylarginine deiminase 2 (PAD2) as being involved in immune system responses during rheumatoid arthritis (RA).

RA is a chronic form of autoimmune arthritis that causes pain and swelling in the wrist and small joints of hands and feet. It affects more than 1.3M adults in the United States according to the American College of Rheumatology.

One hallmark of RA is the production of autoantibodies to proteins that have been post-translationally modified by citrullination, which occurs by enzymatic conversion of arginine residues into citrullines. Anti-citrullinated protein antibodies are present in about 75 percent of people living with RA.

Dr. Shelef's group identified the enzyme PAD2 as contributing to citrullination in a mouse model of RA, thus mediating the severity of RA inflammatory processes and disease manifestations.

The study funded by the Rheumatology Research Foundation will focus on refining our understanding of how PAD2 regulates the ability of people to normally make antibodies to fight disease as well as abnormally develop autoimmune antibodies in rheumatoid arthritis.

Defining the role of PAD2 and citrullination in immunity and autoimmunity will inform the design of novel diagnostics and therapeutics to improve the health of people with rheumatoid arthritis and other rheumatic diseases.

Resources:

• Bawadekar M, Shim D, Johnson CJ, Warner TF, Rebernick R, Damgaard D, Nielsen CH, Pruijn GJM, Nett JE, Shelef MA. 2017. Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation. J Autoimmun. 80:39-47.