Minoru Satoh, MD, PhD, University of Florida

"Posttranslational Modification in Lupus Autoantibody Production"

2007 Novel Pilot Projects Program

Production of autoantibodies to a few nuclear proteins is a characteristic of lupus. However, the mechanisms to specifically select a few targets are not well understood. An intraperitoneal injection (ip) of hydrocarbon oil in normal mice frequently induces autoantibodies to U small nuclear ribonucleoproteins (UsnRNPs). This typically starts from the U1-70K component, which has an unusually high arginine content. A unique enzyme peptidylarginine deiminase (PAD), which can convert arginine residues in proteins into citrulline, is highly expressed in macrophages in pristane-treated mice. We hypothesize that aberrant citrullinated U1-70K proteins produced by PAD may be the trigger of autoimmune response.