van der Meulen Pomme M, Barendregt Anouk M, Cuadrado Eloy, Magro-Checa César, Steup-Beekman Gerda M, Schonenberg-Meinema Dieneke, Van den Berg J Merlijn, Li Quan-Zhen, Baars Paul A, Wouters Diana, Voskuyl Alexandre E, Ten Berge Ineke R J M, Huizinga Tom W J, Kuijpers Taco W
Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital Academic Medical Center.
Astrocyte Biology and Neurodegeneration Group, Netherlands Institute for Neuroscience, Amsterdam.
Rheumatology (Oxford). 2017 Aug 1;56(8):1407-1416. doi: 10.1093/rheumatology/kex073.
The aim was to investigate the association between autoantibodies (autoAbs) and neuropsychiatric (NP) involvement in patients with SLE and to evaluate whether any autoAb or a combination of these autoAbs could indicate the underlying pathogenic process.
Using a multiplexed protein array for 94 antigens, we compared the serum autoAb profiles of 69 NPSLE patients, 203 SLE patients without NP involvement (non-NPSLE) and 51 healthy controls. Furthermore, we compared the profiles of NPSLE patients with clinical inflammatory (n = 38) and ischaemic (n = 31) NP involvement.
In total, 75 IgG and 47 IgM autoAbs were associated with SLE patients in comparison with healthy controls. Comparing NPSLE with non-NPSLE and healthy control sera, 9 IgG (amyloid, cardiolipin, glycoprotein 2, glycoprotein 210, heparin, heparan sulphate, histone H2A, prothrombin protein and vimentin) and 12 IgM (amyloid, cardiolipin, centromere protein A, collagen II, histones H2A and H2B, heparan sulphate, heparin, mitochondrial 2, nuclear Mi-2, nucleoporin 62 and vimentin) autoAbs were present at significantly different levels in NPSLE. The combination of IgG autoAbs against heparan sulphate, histone H2B and vimentin could differentiate NPSLE from non-NPSLE (area under the curve 0.845, 99.97% CI: 0.756, 0.933; P < 0.0001). Compared with non-NPSLE, four IgG and seven IgM autoAbs were significantly associated with inflammatory NPSLE. In ischaemic NPSLE, three IgG and three IgM autoAbs were significantly different from non-NPSLE patients.
In our cohort, the presence of high levels of anti-heparan sulphate and anti-histone H2B combined with low levels of anti-vimentin IgG autoAbs is highly suggestive of NPSLE. These results need to be validated in external cohorts.
本研究旨在调查系统性红斑狼疮（SLE）患者自身抗体（autoAbs）与神经精神（NP）受累之间的关联，并评估是否有任何自身抗体或这些自身抗体的组合能够提示潜在的致病过程。
我们使用针对94种抗原的多重蛋白阵列，比较了69例神经精神性SLE（NPSLE）患者、203例无NP受累的SLE患者（非NPSLE）和51例健康对照者的血清自身抗体谱。此外，我们还比较了有临床炎症性（n = 38）和缺血性（n = 31）NP受累的NPSLE患者的抗体谱。
与健康对照相比，共有75种IgG和47种IgM自身抗体与SLE患者相关。将NPSLE与非NPSLE及健康对照血清进行比较，9种IgG（淀粉样蛋白、心磷脂、糖蛋白2、糖蛋白210、肝素、硫酸乙酰肝素、组蛋白H2A、凝血酶原蛋白和波形蛋白）和12种IgM（淀粉样蛋白、心磷脂、着丝粒蛋白A、胶原蛋白II、组蛋白H2A和H2B、硫酸乙酰肝素、肝素、线粒体2、核Mi-2、核孔蛋白62和波形蛋白）自身抗体在NPSLE中的水平存在显著差异。针对硫酸乙酰肝素、组蛋白H2B和波形蛋白的IgG自身抗体组合可将NPSLE与非NPSLE区分开来（曲线下面积为0.845，99.97%可信区间：0.756，0.933；P < 0.0001）。与非NPSLE相比，4种IgG和7种IgM自身抗体与炎症性NPSLE显著相关。在缺血性NPSLE中，3种IgG和3种IgM自身抗体与非NPSLE患者有显著差异。
在我们的队列中，高水平的抗硫酸乙酰肝素和抗组蛋白H2B以及低水平的抗波形蛋白IgG自身抗体的存在高度提示NPSLE。这些结果需要在外部队列中进行验证。
