M. Segelmark et al., THE PIZ GERME OF ALPHA(1)-ANTITRYPSIN AS A DETERMINANT OF OUTCOME IN PR3-ANCA-POSITIVE VASCULITIS, Kidney international, 48(3), 1995, pp. 844-850
We have previously demonstrated that a strong correlation exists betwe
en systemic vasculitis with proteinase 3-anti-neutrophil cytoplasm ant
ibodies (PR3-ANCA) and heterozygosity for alpha(1)-antitrypsin (alpha(
1)-AT) deficiency, PiZ. In the present study we characterized the PiZ-
positive subgroup by laboratory findings, clinical features and outcom
e. The series studied consisted of 18 PiZ-positive and 81 PiZ-negative
PR3-ANCA patients, comparable in sex ratio, age, C-reactive protein c
oncentrations and renal function at diagnosis, and treatment: PiZ-posi
tive patients had a more disseminated disease as reflected by the numb
er of affected organs (P < 0.01). We found no group differences in rel
apse tendency. Overall mortality was 39% (7 of 18) in the PiZ-positive
and 16% (13 of 81) in the non-PiZ group (P = 0.048). When survival an
alysis was restricted to 66 patients included in the study at disease
onset, the group difference was significant (P = 0.016). The results s
uggest that the subnormal response of plasma (alpha(1)-AT seen in PiZ-
heterozygotes enhances the risk of dissemination of the vasculitic pro
cess and the risk of a fatal outcome. We consider alpha(1)-AT phenotyp
ing to be justified in cases of PR3-ANCA-positive vasculitis. Treatmen
ts decreasing plasma alpha(1)-AT (such as plasmapheresis without plasm
a replacement) may be deleterious.