Nowack R, Grab I, Flores-Suarèz L F, Schnülle P, Yard B, van der Woude F J
Fifth Medical Clinic (Nephrology, Endocrinology), University-Clinic Mannheim, Faculty of Clinical Medicine of the University of Heidelberg, Mannheim, Germany.
Nephrol Dial Transplant. 2001 Aug;16(8):1631-7. doi: 10.1093/ndt/16.8.1631.
Antineutrophil cytoplasmic autoantibodies (ANCA) are presumed to reflect disease-activity and to be useful for guidance of immunosuppressive therapy of ANCA-associated systemic vasculitis (AASV), but with respect to conventional ANCA assays this is controversial. ANCA titres, measured in the IgG3 subclass and modern capture ELISAs, have been said to be superior predictors of relapses of AASV.
In this retrospective study serial measurements of ANCA parameters and soluble CD14 (sCD14) were performed in 169 consecutive sera over a median of 21 months in 18 patients with AASV and related to disease activity, assessed by Birmingham Vasculitis Activity Score (BVAS) for new or deteriorated (BVAS1), and for chronic disease activity (BVAS2). Fourteen patients had Wegener's granulomatosis (WG) and were C-ANCA positive with Pr 3-antibodies and four patients had microscopic polyangiitis (MPA) with P-ANCA and MPO-antibodies. In WG patients ANCA by IIF, Pr 3-ELISA for IgG, IgG1, IgG3, IgG4 and sCD14 were measured, as well as capture ELISA for Pr 3, and in MPA patients ANCA by IIF, MPO-ELISA for IgG and IgG1, IgG3, IgG4, and sCD14 respectively. In eight patients, data collection started at diagnosis, in 10 patients at remission.
The parameters predicted neither the nine major relapses (increase of immunosuppression necessary), nor the 26 minor relapses (increase of BVAS1>2) with sufficient sensitivity (>80%) or specificity (> 90%90%), and they also failed to predict relapses within the following 2 months. ANCA-IgG3 and capture ELISA for Pr 3 were not advantageous for prediction of relapses (sensitivity 0.45 and 0.19 respectively), and sCD14 remained elevated in all samples irrespective of disease activity.
There is no rationale for serial measurements of ANCA in AASV. For changes of therapy, the ANCA parameters should only be used in conjunction with clinical information.
抗中性粒细胞胞浆自身抗体（ANCA）被认为可反映疾病活动度，对ANCA相关系统性血管炎（AASV）的免疫抑制治疗具有指导作用，但对于传统的ANCA检测方法而言，这一点存在争议。据报道，采用IgG3亚类和现代捕获ELISA法检测的ANCA滴度是AASV复发的更好预测指标。
在这项回顾性研究中，对18例AASV患者连续169份血清进行了ANCA参数和可溶性CD14（sCD14）的系列检测，检测时间中位数为21个月，并将其与疾病活动度相关联，疾病活动度通过伯明翰血管炎活动评分（BVAS）评估，包括新发病例或病情恶化（BVAS1）以及慢性病活动度（BVAS2）。14例患者患有韦格纳肉芽肿（WG），C-ANCA阳性且抗蛋白酶3（Pr 3）抗体阳性，4例患者患有显微镜下多血管炎（MPA），P-ANCA和抗髓过氧化物酶（MPO）抗体阳性。对WG患者检测了间接免疫荧光法（IIF）检测的ANCA、Pr 3-ELISA检测的IgG、IgG1、IgG3、IgG4以及sCD14，以及Pr 3捕获ELISA法；对MPA患者分别检测了IIF检测的ANCA、MPO-ELISA检测的IgG和IgG1、IgG3、IgG4以及sCD14。8例患者的数据收集从诊断时开始，10例患者在缓解期开始收集。
这些参数对9次主要复发（需要增加免疫抑制）和26次次要复发（BVAS1增加>2）的预测，其敏感性（>80%）或特异性（>90%）均不足，且也无法预测随后2个月内的复发。ANCA-IgG3和Pr 3捕获ELISA法对复发的预测并无优势（敏感性分别为0.45和0.19），且无论疾病活动度如何，所有样本中的sCD14均保持升高。
在AASV中进行ANCA系列检测并无依据。对于治疗方案的调整，ANCA参数仅应结合临床信息使用。
