University of Michigan, Department of Pathology, Ann Arbor, MI, USA; Safety Sciences, Pfizer Global Research & Development, Ann Arbor, MI, USA.
Proteomics Clin Appl. 2007 Oct;1(10):1212-20. doi: 10.1002/prca.200600906. Epub 2007 Sep 11.
Wegener's Granulomatosis (WG) is an idiopathic granulomatosis autoimmune vasculitis that primarily affects small vessels and is associated with glomerulonephritis and pulmonary granulomatous vasculitis. Anti-neutrophil cytoplasmic auto-antibodies (cANCA) against proteinase-3 are used to identify WG, but ANCA titers are not present in some patients with the localized disease. The objective of this study was to develop an antibody array to help identify protein expression patterns in serum from patients with WG as compared to normals. The arrays were tested for limits of detection, background, and cross reactivity using standard proteins. The arrays were hybridized with either normal patient serum (n = 30) or with serum samples from a population of WG patients (n = 26) that were age and sex matched. Data analysis and curve fitting of the standard dilution series calculated r(2) values and determined a sensitivity of <50 pg/mL for the majority of proteins. A total of 24 proteins were assessed. Several statistically significant increases (p<0.05) were seen in the expression of: angiotensin converting enzyme-I, IFN-γ, IL-8, s-ICAM-1 and s-VCAM in WG patients as compared to controls. Utilizing the antibody microarray technology has led to the identification of potential biomarkers of vascular injury in the serum of WG patients.
韦格纳肉芽肿病（WG）是一种特发性肉芽肿性自身免疫性小血管血管炎，主要影响小血管，与肾小球肾炎和肺肉芽肿性血管炎有关。抗中性粒细胞胞浆抗体（cANCA）针对蛋白酶-3 用于识别 WG，但一些局部疾病患者的 ANCA 滴度并不存在。本研究的目的是开发一种抗体微阵列，以帮助鉴定 WG 患者血清中的蛋白质表达模式与正常人相比。使用标准蛋白测试了阵列的检测限、背景和交叉反应性。将阵列与正常患者血清（n=30）或与年龄和性别匹配的 WG 患者的血清样本（n=26）杂交。对标准稀释系列进行数据分析和曲线拟合，计算 r(2) 值，并确定大多数蛋白质的灵敏度 <50pg/mL。共评估了 24 种蛋白质。与对照组相比，WG 患者的血管紧张素转换酶-I、IFN-γ、IL-8、s-ICAM-1 和 s-VCAM 的表达明显增加（p<0.05）。利用抗体微阵列技术已经鉴定出 WG 患者血清中血管损伤的潜在生物标志物。
