van Rossum A P, Limburg P C, Kallenberg C G
Department of Clinical Immunology, University Hospital Groningen, Hanzeplein 1, The Netherlands.
Clin Exp Rheumatol. 2003 Nov-Dec;21(6 Suppl 32):S64-8.
Antineutrophil cytoplasm autoantibody (ANCA)-associated small vessel vasculitides are systemic diseases characterized by chronic inflammation of blood vessels. These vasculitides are associated with the presence of ANCA which are, in most cases, directed towards proteinase 3 (PR3) or myeloperoxidase (MPO). In vitro and in vivo data have suggested a pathophysiological role in the ANCA-associated vasculitides, particularly based on the capacity of autoantibodies to bind and activate neutrophils. This review focuses on the role of constitutive expression of proteinase 3 on the membrane of resting neutrophils (mPR3). mPR3 can be expressed on the total population or on a subset of neutrophils and levels of mPR3 differ between individuals. The level of mPR3 on resting neutrophils and the percentage of mPR3 expressing neutrophils is stable in time for a given individual, suggesting a genetic determinant. Patients with ANCA-associated vasculitis have an increased constitutive expression of mPR3 on resting neutrophils compared to healthy controls. High levels of mPR3 on resting neutrophils are a risk factor for the development of relapses in patients with PR3-ANCA-associated vasculitis, probably by making resting neutrophils more susceptible for binding ANCA and induction of activation. As such, constitutive mPR3 expression on neutrophils seems another pathogenic factor in ANCA-associated vasculitis.
抗中性粒细胞胞浆自身抗体（ANCA）相关小血管炎是一类以血管慢性炎症为特征的全身性疾病。这些血管炎与ANCA的存在相关，在大多数情况下，ANCA针对蛋白酶3（PR3）或髓过氧化物酶（MPO）。体外和体内数据表明ANCA在相关血管炎中具有病理生理作用，特别是基于自身抗体结合和激活中性粒细胞的能力。本综述重点关注静息中性粒细胞（mPR3）膜上蛋白酶3组成性表达的作用。mPR3可在全部中性粒细胞或中性粒细胞亚群上表达，且个体间mPR3水平存在差异。对于给定个体，静息中性粒细胞上mPR3的水平以及表达mPR3的中性粒细胞百分比在时间上是稳定的，提示存在遗传决定因素。与健康对照相比，ANCA相关血管炎患者静息中性粒细胞上mPR3的组成性表达增加。静息中性粒细胞上高水平的mPR3是PR3-ANCA相关血管炎患者复发的危险因素，可能是因为使静息中性粒细胞更容易结合ANCA并诱导激活。因此，中性粒细胞上mPR3的组成性表达似乎是ANCA相关血管炎的另一个致病因素。
