Rietveld Anke, van den Hoogen Luuk L, Bizzaro Nicola, Blokland Sofie L M, Dähnrich Cornelia, Gottenberg Jacques-Eric, Houen Gunnar, Johannsen Nora, Mandl Thomas, Meyer Alain, Nielsen Christoffer T, Olsson Peter, van Roon Joel, Schlumberger Wolfgang, van Engelen Baziel G M, Saris Christiaan G J, Pruijn Ger J M
Department of Neurology, Center for Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
Laboratory of Translational Immunology, Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2018 Jun 5;9:1200. doi: 10.3389/fimmu.2018.01200. eCollection 2018.
Autoantibodies to cytosolic 5'-nucleotidase 1A (cN-1A; NT5C1A) have a high specificity when differentiating sporadic inclusion body myositis from polymyositis and dermatomyositis. In primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE) anti-cN-1A autoantibodies can be detected as well. However, various frequencies of anti-cN-1A reactivity have been reported in SLE and pSS, which may at least in part be explained by the different assays used. Here, we determined the occurrence of anti-cN-1A reactivity in a large number of patients with pSS and SLE using one standardized ELISA.
Sera from pSS ( = 193) and SLE patients ( = 252) were collected in five European centers. Anti-cN-1A, anti-Ro52, anti-nucleosome, and anti-dsDNA reactivities were tested by ELISA (Euroimmun AG) in a single laboratory. Correlations of anti-cN-1A reactivity with demographic data and clinical data (duration of disease at the moment of serum sampling, autoimmune comorbidity and presence of muscular symptoms) were analyzed using SPSS software.
Anti-cN-1A autoantibodies were found on average in 12% of pSS patients, with varying frequencies among the different cohorts (range: 7-19%). In SLE patients, the anti-cN-1A positivity on average was 10% (range: 6-21%). No relationship was found between anti-cN-1A reactivity and the presence or absence of anti-Ro52, anti-nucleosome, and anti-dsDNA reactivity in both pSS and SLE. No relationship between anti-cN-1A reactivity and duration of disease at the moment of serum sampling and the duration of serum storage was observed. The frequency of muscular symptoms or viral infections did not differ between anti-cN-1A-positive and -negative patients. In both disease groups anti-cN-1A-positive patients suffered more often from other autoimmune diseases than the anti-cN-1A-negative patients (15 versus 5% ( = 0.05) in pSS and 50 versus 30% ( = 0.02) in SLE).
Our results confirm the relatively frequent occurrence of anti-cN-1A in pSS and SLE patients and the variation in anti-cN-1A reactivity between independent groups of these patients. The explanation for this variation remains elusive. The correlation between anti-cN-1A reactivity and polyautoimmunity should be evaluated in future studies. We conclude that anti-cN-1A should be classified as a myositis-associated-, not as a myositis-specific-autoantibody based on its frequent presence in SLE and pSS.
胞质5'-核苷酸酶1A(cN-1A;NT5C1A)自身抗体在鉴别散发性包涵体肌炎与多发性肌炎和皮肌炎时具有高度特异性。在原发性干燥综合征(pSS)和系统性红斑狼疮(SLE)中也可检测到抗cN-1A自身抗体。然而,在SLE和pSS中报道的抗cN-1A反应性频率各不相同,这至少部分可以用所使用的不同检测方法来解释。在此,我们使用一种标准化酶联免疫吸附测定(ELISA)法确定了大量pSS和SLE患者中抗cN-1A反应性的发生率。
在欧洲的五个中心收集了pSS患者(n = 193)和SLE患者(n = 252)的血清。抗cN-1A、抗Ro52、抗核小体和抗双链DNA(dsDNA)反应性在单个实验室中通过ELISA法(欧蒙医学诊断有限公司)进行检测。使用SPSS软件分析抗cN-1A反应性与人口统计学数据和临床数据(血清采样时的疾病持续时间、自身免疫性合并症和肌肉症状的存在情况)之间的相关性。
平均12%的pSS患者检测到抗cN-1A自身抗体,不同队列中的频率有所不同(范围:7%-19%)。在SLE患者中,抗cN-1A阳性率平均为10%(范围:6%-21%)。在pSS和SLE患者中,均未发现抗cN-1A反应性与抗Ro52、抗核小体和抗dsDNA反应性的存在与否之间存在关联。未观察到抗cN-1A反应性与血清采样时的疾病持续时间以及血清储存时间之间的关系。抗cN-1A阳性和阴性患者之间肌肉症状或病毒感染的频率没有差异。在这两种疾病组中,抗cN-1A阳性患者比抗cN-1A阴性患者更常患有其他自身免疫性疾病(pSS中分别为15%对5%(p = 0.05),SLE中分别为50%对30%(p = 0.02))。
我们的结果证实了抗cN-1A在pSS和SLE患者中相对频繁出现,以及这些患者的独立组之间抗cN-1A反应性的差异。这种差异的原因仍然难以捉摸。抗cN-1A反应性与多自身免疫性之间的相关性应在未来的研究中进行评估。我们得出结论,基于抗cN-1A在SLE和pSS中频繁存在,应将其归类为与肌炎相关的自身抗体,而非肌炎特异性自身抗体。