Alpha 1- antitrypsin (AAT) is a major inhibitor of proteinase 3. In one with AAT deficiency, it has been postulated that there may be an increase in proteinase 3 activity due to inability of AAT to inactivate the proteinase 3. This imbalance may lead to ANCA vasculitis. See below for some interesting aspects of this association. One study looked at an association of the allele of AAT deficiency and relation to ANCA disease. While a cause and effect cannot be proven, this is an interesting association. As early as 1993, this assocaition was encountered and studied. Interestingly, another study that looked at AAT inhibitor phenotypes and levels examined in 40 ANCA positive cases of systemic vasculitis, an excess of PiZ and PiS alleles were associated with the development of pulmonary haemorrhage and alpha-1-proteinase inhibitor levels were lower in the subgroup with pulmonary haemorrhage. However, this allelic imbalance and reduced alpha-1-proteinase inhibitor level was not confined to antiproteinase 3 positive patients and did not appear to be associated with other organ involvement or disease severity.
-Mala Sachdeva, MD