ALPHA(1)-ANTITRYPSIN PHENOTYPES IN PATIENTS WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-POSITIVE VASCULITIS

1. The genetic background of anti-neutrophil cytoplasmic antibody (ANC A)-associated systemic vasculitis remains largely unknown, Recently a very high prevalence of medium and severe deficiency of alpha(1)-antit rypsin was described in a small group of patients with Wegener's granu lomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and alpha(1)-antitrypsin is the main inhibitor of this enzyme. 2. alp ha(1)-Antitrypsin phenotypic polymorphism was determined by isoelectri c focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyar teritis and one suffered from idiopathic rapidly progressive glomerulo nephritis. 3. Two patients were homozygous PiZZ and three were heteroz ygous PiMZ. These phenotype frequencies differed significantly from ex pected values, assuming Hardy-Weinberg equilibrium (P<0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P<0.00 1). 4. Furthermore, the serum of 47 patients with severe alpha(1)-anti trypsin deficiency (PiZZ) was tested for the presence of ANCA. All ser a were negative for c-ANCA and p-ANCA. None of the patients showed cli nical signs of systemic vasculitis. 5. In conclusion, these data indic ate that alpha(1)-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease.