Audrain M A, Sesboüé R, Baranger T A, Elliott J, Testa A, Martin J P, Lockwood C M, Esnault V L
Immunology Department, Hôtel Dieu, Nantes, France.
Nephrol Dial Transplant. 2001 Jan;16(1):39-44. doi: 10.1093/ndt/16.1.39.
ANCA are autoantibodies directed against polymorphonuclear cell antigens, mainly proteinase 3 (PR3) and myeloperoxidase (MPO), which are implicated in the pathogenesis of small-vessel necrotizing vasculitis. Alpha1-antitrypsin is the main inhibitor of neutral serine proteinase [i.e. human leukocyte elastase (HLE) and PR3] present in PMN alpha-granules (alphaGr). An association first reported by us between PR3 ANCA and the deficient PiZZ phenotype in ANCA-positive systemic vasculitis, now widely confirmed by others, led us to study the incidence and specificity of ANCA among PiZZ subjects.
We tested a population of 191 PiZZ (273 sera) for ANCA activity versus 272 PiMM matched control subjects using alphaGr or antigen-specific ELISA [PR3, HLE, MPO, lactoferin (LF) and bactericidal/ permeability increasing protein (BPI)].
The incidence of antibodies directed against alphaGr and HLE but not PR3, MPO, LF or BPI was increased in the PiZZ as compared to the PiMM group (Fisher probability respectively P < 0.0001 and P < 0.05).
ANCA not directed against classical antigens (MPO and PR3) may be found in PiZZ patients. However, these patients do not develop systemic vasculitis features. Therefore, alpha1-antitrypsin deficiency is not sufficient to induce ANCA positive vasculitides, and may only act as a second hit amplifying factor.
抗中性粒细胞胞浆抗体（ANCA）是针对多形核细胞抗原的自身抗体，主要是蛋白酶3（PR3）和髓过氧化物酶（MPO），它们与小血管坏死性血管炎的发病机制有关。α1-抗胰蛋白酶是存在于中性粒细胞α颗粒（αGr）中的中性丝氨酸蛋白酶[即人白细胞弹性蛋白酶（HLE）和PR3]的主要抑制剂。我们首次报道的PR3 ANCA与ANCA阳性系统性血管炎中PiZZ缺陷表型之间的关联，现已被其他人广泛证实，这促使我们研究PiZZ受试者中ANCA的发生率和特异性。
我们使用αGr或抗原特异性酶联免疫吸附测定法[PR3、HLE、MPO、乳铁蛋白（LF）和杀菌/通透性增加蛋白（BPI）]，对191名PiZZ受试者（273份血清）进行ANCA活性检测，并与272名PiMM匹配对照受试者进行比较。
与PiMM组相比，PiZZ组中针对αGr和HLE而非PR3、MPO、LF或BPI的抗体发生率增加（Fisher概率分别为P < 0.0001和P < 0.05）。
在PiZZ患者中可能发现不针对经典抗原（MPO和PR3）的ANCA。然而，这些患者并未出现系统性血管炎特征。因此，α1-抗胰蛋白酶缺乏不足以诱发ANCA阳性血管炎，可能仅作为一种二次打击放大因子起作用。
