α1-Antitrypsin (AAT) deficiency and ANCA-positive systemic vasculitis: genetic and clinical implications

A high incidence of α1‐antitrypsin (AAT) deficiency has been reported in patients with C‐ANCA systemic vasculitis in association with antibodies against proteinase‐3 (PR3). To clarify the role of AAT deficiency in the acute vasculitic process as well as in progression of the disease, we studied 84 patients with either C‐ANCA or P‐ANCA vasculitis with special reference to: (a) the AAT gene, (b) the phenotypic (Pi) variants and (c) the serum levels during both acute illness and remission. The PiZ gene was found in six patients (8% vs. 1.5% controls) irrespective of the type of autoantibodies (C‐ANCA vs. P‐ANCA). All PiZ patients displayed the ability to raise their AAT serum levels up to the normal range during acute illness. In contrast, 24 patients with the PiM phenotype presented low AAT serum levels during acute illness. In all these patients, the AAT levels returned to normal values during the remission. Low AAT levels were associated with low levels of C‐reactive protein (PCR) (P