Objective

To investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients.

Methods

Anti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences.

Results

We included 101 AAV patients (females 58%, median age 60[51–69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner.

Conclusions

Anti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.

中文翻译：

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IgG 抗 Pentraxin 3 抗体是 ANCA 相关性血管炎的新型生物标志物，可更好地识别嗜酸性肉芽肿伴多血管炎患者

客观的

调查抗中性粒细胞胞浆抗体 (ANCA) 相关性血管炎 (AAV) 患者血清中抗 Pentraxin 3 (PTX3) 抗体的患病率。

方法

抗 PTX3 和 PTX3 水平通过酶联免疫吸附试验分析来自未经选择的 AAV 患者的血清，并与患有系统性红斑狼疮（SLE，n = 130）、其他结缔组织疾病（CTD，n = 97）和匹配的患者进行比较健康对照（n = 97）。通过 ROC 曲线分析确定阳性抗 PTX3 抗体的光密度 (OD) 截止值并设置为 0.234。固定的人粒细胞上的间接免疫荧光 (IIF) 用于分析抗 PTX3 抗体的荧光模式。进行液相抑制测试以评估潜在的干扰。

结果

我们纳入了 101 名 AAV 患者（女性 58%，中位年龄 60[51-69] 岁），患有肉芽肿性多血管炎（GPA，n = 51）、显微镜下多血管炎（MPA，n = 12）或嗜酸性肉芽肿性多血管炎（EGPA） , n = 38)。在 29.7% 的 AAV 患者中检测到抗 PTX3 抗体，显着高于健康对照组 (p < 0.001) 和 CTD (p = 0.030)，但低于 SLE (p = 0.004)。EGPA 中的抗 PTX3 抗体流行率为 44.7%，MPA 中为 25%，GPA 中为 19%（p = 0.034）。在 ANCA 阴性患者中，35.7% 显示出阳性抗 PTX3 抗体。抗 PTX3 与全身 (p = 0.002)、耳鼻喉 (p = 0.006) 和肾脏表现 (p = 0.016) 的较低患病率相关。抗 PTX3 抗体的特征在于固定粒细胞上的特定 IIF 模式。PTX3 血清水平导致 AAV 低于健康对照组 (p < 0.001)。PTX3 以剂量依赖性方式抑制抗 PTX3 结合。

结论

抗 PTX3 自身抗体似乎是一种很有前途的新型 AAV 生物标志物，尤其是 EGPA。