That contrarian view of autoimmunity is based on growing clinical, biological, and structural evidence around a family of enzymes called protein arginine deiminases (PADs). Under normal conditions, PADs live inside cells and modify proteins by changing an arginine to a citrulline. But if they escape their normal environment—for example, when a smoker takes a puff and injured or dying airway cells leak PADs—they set to work on proteins they were never meant to see. Immune cells respond, and over time, antibodies to citrullinated proteins build. Eventually the immune system goes crazy and attacks normal tissues too. Protein citrullination is linked to a host of diseases, including rheumatoid arthritis, lupus, and multiple sclerosis. For example, antibodies to citrullinated proteins show up a decade before a rheumatoid arthritis patient walks into the doctor’s office with joint pain.
by Lisa M. Jarvis |
November 02, 2015