Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay
Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay
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DOI：
10.1177/0961203316640918
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发表时间：
2016-07-01
期刊：
影响因子：
2.6
通讯作者：
Fritzler, M. J.
中科院分区：
文献类型：
--
作者：
Mahler, M.;Swart, A.;Fritzler, M. J.
背景 据报道，患有系统性自身免疫性风湿病的患者体内出现了针对 Ku 的自身抗体，Ku 是一种丰富的具有 DNA 解旋酶活性的核蛋白。人们对抗 Ku 抗体的临床关联知之甚少，尤其是在使用新型诊断技术时。本研究的目的是使用新型化学发光免疫测定法分析不同医疗条件下抗 Ku 抗体的流行情况。 患者和方法 系统性红斑狼疮 (SLE, n=305)、系统性硬化症 (SSc, n=70) 和自身免疫性肌炎 (AIM, n=109) 成人患者的血清样本是本研究的主要焦点。将结果与疾病对照（类风湿性关节炎，RA，n=30；传染病，n=17）和健康个体（n=167）进行比较。此外，还对转诊至风湿病诊所的患者 (n=1078) 提交用于常规自身抗体检测的样本进行了研究。使用全长重组人 Ku，通过 QUANTA Flash Ku 化学发光免疫分析（仅供研究使用，Inova Diagnostics，圣地亚哥，美国）测试所有样品的抗 Ku 抗体。 SLE 患者样本还检测了其他自身抗体。通过回顾性图表审查获得抗Ku抗体阳性患者（高滴度）的临床数据。 结果和发现在疾病队列中，分别有30/305（9.8％）SLE、3/70（4.3％）系统性硬化症和4/109（3.7％）自身免疫性肌炎（AIM）患者呈阳性。四名 AIM 阳性患者患有重叠肌炎综合征，其中包括两名 SLE 患者。三个系统性硬化症 (SSc) 阳性样本诊断为 SSc/SLE 重叠、弥漫性皮肤 SSc 和早期水肿期 SSc。在对照队列中，2/170 (1.2%) 健康个体（均为低滴度）、0/30 (0.0%) (RA) 和 0/17 (0.0%) 传染病患者呈阳性。曲线下面积值分别为：SLE 与对照相比为 0.75，SSc 与对照相比为 0.68，AIM 与对照相比为 0.37。在风湿病诊所转诊队列中，12/1078 (1.1%) 的抗 Ku 抗体呈阳性，其中 9 例呈低滴度，3 例呈高滴度。 3名高阳性抗Ku阳性患者的诊断为：疑似SLE、混合结缔组织病(MCTD)和ANA阳性RA。结论化学发光免疫分析法检测到的抗Ku抗体在SLE中最为常见。当在 AIM 和 SSc 中发现时，它们与重叠综合征和早期 SSc 相关。
Background Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay.Patients and methods Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review.Results and findings In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. controls. In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA.Conclusion Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.