Published
What we have learned about ANCA vasculitis
Condition: ANCA-associated vasculitis (AAV)
Evidence badge: Strong mechanistic link; clinical benefit unproven (no clinical trials of AAT for AAV)
ANCA vasculitis is a disease in which switched-on neutrophils, a type of white blood cell, damage small blood vessels, most often in the lungs, airways, and kidneys. Its link to alpha-1 antitrypsin (AAT) is strong in the lab and in human genetics; whether AAT helps has not been tested in clinical trials.
What we know
The immune system makes antibodies (ANCA) that switch on neutrophils. Neutrophils carry strong enzymes, including elastase and proteinase 3, which normally help fight germs. AAT is the body's "brake" protein for these enzymes. It keeps them from harming healthy tissue.
Genetic studies of DNA from thousands of volunteers found that the AAT gene is linked to one form of this disease, the form where the immune system targets proteinase 3. That is the very enzyme AAT normally holds in check. People who carry the "Z" version of the AAT gene show up more often among those who have it. No clinical trials have tested AAT as a treatment for ANCA vasculitis.
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.
Disclaimer: For education only; not medical advice. Plasma AAT is FDA-approved only for adults with severe AATD and emphysema; other uses are investigational. Talk with your doctor about testing.
References
PubMed-verified: 18 October 2026
- Esnault VL, et al. Kidney Int. 1993;43(6):1329-32. · PMID 8315946 · human · PubMed
- Kitching AR, et al. Nat Rev Dis Primers. 2020;6(1):71. · PMID 32855422 · review · PubMed
- Kessenbrock K, et al. Nat Med. 2009;15(6):623-5. · PMID 19448636 · cell culture + human · PubMed
- Schreiber A, et al. J Am Soc Nephrol. 2012;23(3):470-82. · PMID 22241891 · animal (mouse) · PubMed
- Lyons PA, et al. N Engl J Med. 2012;367(3):214-23. · PMID 22808956 · human genetics (GWAS) · PubMed
- Merkel PA, et al. Arthritis Rheumatol. 2017;69(5):1054-1066. · PMID 28029757 · human genetics (GWAS) · PubMed
- Morris H, et al. Ann Rheum Dis. 2011;70(10):1851-6. · PMID 21821620 · human + cell culture · PubMed
- Clark RA, et al. J Biol Chem. 1981;256(7):3348-53. · PMID 6162845 · cell culture/biochemical · PubMed