Department of Medicine, Cardiology, Deutsches Herzzentrum Berlin, Germany.
Clin Exp Rheumatol. 2010 Jan-Feb;28(1 Suppl 57):62-6.
Anti-neutrophil antibodies (ANCA)-associated vasculitides (AAV) comprise different forms of small vessel vasculitis characterised by B-cell driven autoimmune processes and endothelial cell activation. Aim of this study was to correlate markers of B- and endothelial cell activation with clinical manifestations of disease in AAV.
Consecutive serum samples of patients fulfilling the Chapel Hill Consensus Conference (CHCC) and American College of Rheumatology (ACR) criteria for AAV and healthy donors were used for the determination of ANCA, B-lymphocyte stimulator (BLyS), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) levels using enzyme-linked immunosorbent assay (ELISA). Subset and follow-up analyses were performed in cytoplasmatic ANCA (C-ANCA) or perinuclear ANCA (P-ANCA) positive patients with respect to change in ANCA-titres during the course of disease.
Levels of sVCAM-1 were elevated in all patient groups with vasculitis compared to healthy controls. In contrast, significantly increased levels of BLyS were only observed in patients with Wegener's granulomatosis (WG), but not in patients with microscopic polyangiitis (mPAN)/Churg-Strauss-syndrome (CSS). Remarkably, there were no differences in the levels of sE-selectin between the vasculitis groups and healthy controls. In follow-up analysis, a significant correlation was shown for sE-Selectin and P-ANCA titres as well as sVCAM-1 levels. Furthermore, a strong correlation was detected for sVCAM-1 and creatinine levels. Interestingly, sE-selectin levels and C-ANCA titres were negatively correlated.
Enhanced levels of sVCAM-1 represent a marker for endothelial cell activation in AAV. The observed correlation between sVCAM-1 and creatinine levels might indicate the influence of the vasculitic process on renal function. Signalling pathways for B-cells provided by BLyS could play a significant role in the pathogenesis of WG.
抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）包括不同形式的小血管血管炎，其特征是 B 细胞驱动的自身免疫过程和内皮细胞激活。本研究的目的是将 B 细胞和内皮细胞激活的标志物与 AAV 的疾病临床表现相关联。
使用酶联免疫吸附试验（ELISA）连续检测符合 Chapel Hill 共识会议（CHCC）和美国风湿病学会（ACR）AAV 标准的患者和健康供体的血清样本，以确定 ANCA、B 淋巴细胞刺激物（BLyS）、可溶性血管细胞黏附分子-1（sVCAM-1）和可溶性 E-选择素（sE-selectin）水平。针对疾病过程中 ANCA 滴度的变化，对细胞质性 ANCA（C-ANCA）或核周性 ANCA（P-ANCA）阳性患者进行亚组和随访分析。
与健康对照组相比，所有血管炎患者组的 sVCAM-1 水平均升高。相比之下，仅在 Wegener 肉芽肿（WG）患者中观察到 BLyS 水平显著升高，但在显微镜下多血管炎（mPAN）/Churg-Strauss 综合征（CSS）患者中未观察到。值得注意的是，血管炎组与健康对照组之间 sE-选择素水平没有差异。在随访分析中，sE-选择素与 P-ANCA 滴度以及 sVCAM-1 水平呈显著相关。此外，还检测到 sVCAM-1 与肌酐水平之间的强相关性。有趣的是，sE-选择素水平与 C-ANCA 滴度呈负相关。
sVCAM-1 水平升高代表 AAV 中内皮细胞激活的标志物。观察到的 sVCAM-1 与肌酐水平之间的相关性可能表明血管炎过程对肾功能的影响。BLyS 提供的 B 细胞信号通路可能在 WG 的发病机制中发挥重要作用。
