Muller Kobold A C, Kallenberg C G, Tervaert J W
Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
Br J Rheumatol. 1998 Aug;37(8):901-7. doi: 10.1093/rheumatology/37.8.901.
Wegener's granulomatosis (WG) is an inflammatory disorder characterized by granulomatous inflammation and vasculitis, and is strongly associated with antineutrophil cytoplasmic antibodies (ANCA). ANCA in patients with WG are directed against proteinase 3 (Pr3) in most of the cases. In vitro, upon neutrophil priming, ANCA antigens are expressed on the cell surface, thereby becoming available for interaction with ANCA. Subsequently, these neutrophils become activated. Since ANCA can only interact with leucocytes when the ANCA antigens are present on the cell surface, we questioned whether Pr3 is already expressed on the membranes of circulating granulocytes and monocytes of patients with WG, and whether Pr3 expression is related to disease activity, so explaining the systemic nature and severity of the disease. The expression of Pr3, and other ANCA antigens, i.e. myeloperoxidase (MPO) and human leucocyte elastase (HLE), was analysed on circulating granulocytes and monocytes by flow cytometry, using a non-activating whole-blood method. Disease activity was quantitated using the Birmingham Vasculitis Activity Score (BVAS). Seventeen patients with active WG and anti-Pr3 antibodies were included in this study. Nine of these patients were also analysed at the time of remission. Twelve patients with sepsis served as positive controls, and 10 healthy volunteers as negative controls for granulocyte/monocyte activation. Pr3 expression on neutrophils was increased in patients with active WG compared to patients with quiescent disease and healthy controls. On monocytes, no differences in Pr3 expression were found between those groups. Furthermore, the expression of MPO and HLE did not differ between patient groups and healthy controls. Upon follow-up, the expression of Pr3 on neutrophils from patients with active WG decreased when patients went into remission. Pr3 expression on neutrophils correlated with the BVAS score (r = 0.40, P < 0.05). In conclusion, circulating neutrophils from patients with active WG have increased expression of Pr3. In addition, the expression of Pr3 correlates with disease activity, suggesting that the availability of Pr3 for interaction with ANCA plays a central role in the disease process.
韦格纳肉芽肿病（WG）是一种以肉芽肿性炎症和血管炎为特征的炎症性疾病，与抗中性粒细胞胞浆抗体（ANCA）密切相关。大多数WG患者的ANCA针对蛋白酶3（Pr3）。在体外，中性粒细胞被激活后，ANCA抗原在细胞表面表达，从而可与ANCA相互作用。随后，这些中性粒细胞被激活。由于只有当ANCA抗原存在于细胞表面时，ANCA才能与白细胞相互作用，我们推测Pr3是否已经在WG患者循环中的粒细胞和单核细胞膜上表达，以及Pr3的表达是否与疾病活动相关，从而解释该疾病的全身性本质和严重性。采用非激活全血法，通过流式细胞术分析循环中的粒细胞和单核细胞上Pr3以及其他ANCA抗原，即髓过氧化物酶（MPO）和人白细胞弹性蛋白酶（HLE）的表达。使用伯明翰血管炎活动评分（BVAS）对疾病活动进行量化。本研究纳入了17例患有活动性WG且有抗Pr3抗体的患者。其中9例患者在缓解期也进行了分析。12例脓毒症患者作为阳性对照，10名健康志愿者作为粒细胞/单核细胞激活的阴性对照。与病情静止的患者和健康对照相比，活动性WG患者中性粒细胞上Pr3的表达增加。在单核细胞上，这些组之间未发现Pr3表达的差异。此外，患者组和健康对照之间MPO和HLE的表达没有差异。随访时，活动性WG患者病情缓解时，其中性粒细胞上Pr3的表达下降。中性粒细胞上Pr3的表达与BVAS评分相关（r = 0.40，P < 0.05）。总之，活动性WG患者循环中的中性粒细胞Pr3表达增加。此外，Pr3的表达与疾病活动相关，表明Pr3与ANCA相互作用的可及性在疾病过程中起核心作用。
