Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis
Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis
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DOI：
10.1186/s13075-019-1839-5
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发表时间：
2019-02-14
影响因子：
4.9
通讯作者：
Nikpour, Mandana
中科院分区：
文献类型：
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作者：
Moxey, Jayne;Huq, Molla;Nikpour, Mandana
高达12%的系统性硬化症（SSc）患者有抗中性粒细胞胞浆抗体（ANCA）。然而，这些患者中的大多数没有表现出ANCA相关性血管炎（AAV）， ANCA在这些患者中的意义尚不清楚。本研究的目的是确定ANCA在特征明确的SSc队列中的患病率，并检查ANCA与SSc临床特征、其他自身抗体、治疗和死亡率之间的关系。临床数据来自澳大利亚硬皮病队列研究（ASCS）的5个中心。ANCA阳性定义为存在细胞质ANCA （c-ANCA）、核周ANCA （p-ANCA）、非典型ANCA、抗髓过氧化物酶（抗mpo）或抗蛋白酶-3（抗pr3）的任何一种或组合。人口统计学和临床特征与ANCA的关系通过逻辑或线性回归进行调查。生存率分析采用Kaplan-Meyer曲线和Cox回归模型。1303例患者中，116例（8.9%）为ANCA阳性。抗pr3比抗mpo更常见（分别占anca阳性患者的13.8%和11.2%）。只有3例anca阳性患者有AAV。抗scl -70在ANCA阳性与ANCA阴性患者（25% vs 12.8%, p < 0.001）、抗mpo阳性与抗mpo阴性患者（38.5% vs 13.6%, p = 0.006）和抗pr3阳性与抗pr3阴性患者（44.4% vs 13.4%, p < 0.001）中更为常见。ANCA阳性组（44.8% vs 21.8%, p < 0.001）和抗pr3阳性组（50.0% vs 23.4%, p = 0.009）间质性肺疾病（ILD）患病率较高。在多变量分析中，调整抗scl -70抗体后，anca阳性状态仍与ILD相关。肺栓塞（PE）在anca阳性患者（8.6% vs 3.0%, p = 0.002）和抗pr3阳性患者（16.7% vs 3.3%, p = 0.022）中更为常见。在抗磷脂抗体调整后的多变量分析中，anca阳性状态仍然与PE相关。Kaplan-Meier分析显示，anca阳性患者的死亡率增加（p = 0.006）。在Cox回归分析中，在调整年龄和性别后，ANCA与死亡率增加相关。ANCA与SSc中ILD和PE患病率增加有关。ANCA应该在SSc中进行测试，因为它可以识别预后较差的个体，需要密切监测不良后果。
Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality.Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models.Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex.ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.