Microscopic polyangiitis

Microscopic polyangiitis (MPA) is a rare vasculitis that inflames small blood vessels, mostly in the kidneys and lungs. Neutrophils, a type of white blood cell, are central to it; evidence for alpha-1 antitrypsin (AAT) is mixed.

What we know

In most people with MPA, the immune system makes antibodies against myeloperoxidase (MPO), an enzyme inside neutrophils. These antibodies switch neutrophils on, and switched-on neutrophils can injure vessel walls and release web-like "traps" (NETs). Neutrophils also carry the enzymes elastase and proteinase 3. AAT is the body's "brake" for those two enzymes; it does not block MPO.

In mice, immune cells lacking elastase and proteinase 3, the two enzymes AAT normally holds in check, protected the kidneys from MPO-type damage. In people, the AAT gene link seen in the PR3 form of ANCA vasculitis has not been found in the MPO form most people with MPA have. No clinical trials have tested AAT as a treatment for microscopic polyangiitis.

About this series: Mark Egly diagnosed his own alpha-1 antitrypsin deficiency at age 62. After learning he had emphysema and COPD despite never smoking, he connected the dots himself, and testing confirmed it. That discovery set the Foundation on the path of tracing AAT's possible links to conditions like this one.