Nephrol Dial Transplant (1996) 11: 438-443
© 1996 European Renal Association-European Dialysis and Transplant Association
research-article
C-antineutrophil cytoplasmic antibody positivity in vasculitis patients is associated with the Z allele of alpha-1-antitrypsin, and P-antineutrophil cytoplasmic antibody positivity with the S allele
1Renal Unit, Royal Postgraduate Medical School, Hammersmith Hospital London, UK 2MRC Human Biochemical Genetics Unit, The Galton Laboratory, University College London London, UK
Correspondence and offprint requests to: Correspondence and offprint requests to: Dr M. E. Griffith, Renal Unit, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK
BACKGROUND.: Antineutrophil cytoplasmic antibodies (ANCA) in vasculitis have either cANCA or pANCA patterns as defined by immunofluorescence. The target autoantigen of cANCA is usually proteinase 3 (PR3), whereas that of pANCA is usually myeloperoxidase (MPO). Alpha-1-antitrypsin (
1AT) is the major physiological inhibitor of PR3, while MPO is an inhibitor of 1AT.
METHODS.: To determine whether there was an association between ANCA positive vasculitis, ANCA pattern, and 1AT deficiency alleles, we studied 1AT phenotypes of 99 cANCA and 99 pANCA positive vasculitis patients by isoelectric focusing and immunoblotting, and compared them with 2310 controls from the same geographical area.
RESULTS.: C-ANCA patients showed an increased frequency of the Z allele (0.055 versus 0.018 in controls), conferring a relative risk of 3. They showed no increase in frequency of the S allele. P-ANCA patients showed an increased frequency of the S allele (0.091 versus 0.046 in controls) conferring a relative risk of 2. The frequency of the Z allele also appeared to be increased (0.030 versus 0.018 in controls), but this was not statistically significant.
CONCLUSIONS.: These findings demonstrate an association between ANCA-positive vasculitis and deficiency phenotypes of 1AT, and suggest a role for 1AT in the development of systemic vasculitis.
Keywords: alpha-1-antitrypsin; ANCA; autoimmunity; myeloperoxidase; proteinase 3; systemic vasculitis; vasculitis
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