Griffith M E, Lovegrove J U, Gaskin G, Whitehouse D B, Pusey C D
Renal Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Nephrol Dial Transplant. 1996 Mar;11(3):438-43.
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 (alpha 1AT) is the major physiological inhibitor of PR3, while MPO is an inhibitor of alpha 1AT.
To determine whether there was an association between ANCA positive vasculitis, ANCA pattern, and alpha 1AT deficiency alleles, we studied alpha 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.
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.
These findings demonstrate an association between ANCA-positive vasculitis and deficiency phenotypes of alpha 1AT, and suggest a role for alpha 1AT in the development of systemic vasculitis.
血管炎中的抗中性粒细胞胞浆抗体（ANCA）通过免疫荧光法可呈现胞浆型ANCA（cANCA）或核周型ANCA（pANCA）模式。cANCA的靶自身抗原通常是蛋白酶3（PR3），而pANCA的靶自身抗原通常是髓过氧化物酶（MPO）。α1抗胰蛋白酶（α1AT）是PR3的主要生理性抑制剂，而MPO是α1AT的抑制剂。
为确定ANCA阳性血管炎、ANCA模式与α1AT缺乏等位基因之间是否存在关联，我们通过等电聚焦和免疫印迹研究了99例cANCA阳性和99例pANCA阳性血管炎患者的α1AT表型，并将其与来自同一地理区域的2310名对照进行比较。
cANCA患者中Z等位基因频率增加（对照组为0.018，患者组为0.055），相对风险为3。S等位基因频率未增加。pANCA患者中S等位基因频率增加（对照组为0.046，患者组为0.091），相对风险为2。Z等位基因频率似乎也有所增加（对照组为0.018，患者组为0.030），但无统计学意义。
这些发现表明ANCA阳性血管炎与α1AT缺乏表型之间存在关联，并提示α1AT在系统性血管炎的发生发展中起作用。
