Autoimmunity occurs when the body’s immune system mistakenly attacks and destroys healthy tissue. Around 10% of the population is affected by autoimmune disease, which bears direct healthcare costs of $100 billion in the US alone, with similar estimates in Europe.
One such condition is AAV, which stands for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. There is no safe, effective treatment for AAV. Vasculitis causes blood vessel injury, which can damage several organs and systems, predominantly the kidneys, skin, respiratory system and digestive system. AAV occurs when antibodies, molecules secreted by the body to fend off invading moecules (eg bacteria), instead attack specific proteins found in two types of human immune cell: neutrophils and monocytes. Binding of the antibody to its corresponding protein alters intracellular signaling pathways, causing the immune cells to attack small and medium blood vessels. This leads to chronic inflammation and damage of the vessels.
One protein targeted by antibodies in AAV is myeloperoxidase (MPO). The role of MPO in the body is to produce a specific acid. In an acidic environment, MPO binds more readily to its antibody. As such, the activity of MPO may drive inflammation in AAV. This project will examine the effects of blocking MPO’s activity in monocytes that have been exposed to the diseased antibodies. The data collected will contribute to a larger body of work that aims to define monocyte response to activation by antibodies in AAV and how blocking certain molecules and pathways may provide the basis for new therapies.
