Loebel Madlen, Eckey Maren, Sotzny Franziska, Hahn Elisabeth, Bauer Sandra, Grabowski Patricia, Zerweck Johannes, Holenya Pavlo, Hanitsch Leif G, Wittke Kirsten, Borchmann Peter, Rüffer Jens-Ulrich, Hiepe Falk, Ruprecht Klemens, Behrends Uta, Meindl Carola, Volk Hans-Dieter, Reimer Ulf, Scheibenbogen Carmen
Institute of Medical Immunology, Charité University Medicine Berlin, Campus Virchow, Berlin, Germany.
JPT Peptide Technologies GmbH, Berlin, Germany.
PLoS One. 2017 Jun 12;12(6):e0179124. doi: 10.1371/journal.pone.0179124. eCollection 2017.
Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.
We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.
EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.
Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry.
爱泼斯坦-巴尔病毒（EBV）作为多种自身免疫性疾病的触发因素或辅助因子发挥着重要作用。在一部分慢性疲劳综合征（CFS）患者中，疾病始于传染性单核细胞增多症，这是一种晚期原发性EBV感染，而在另一部分患者中可观察到EBV特异性抗体水平的改变。
我们使用微阵列平台，对50名健康对照者和92名CFS患者针对EBV的IgG反应进行了全面分析。多发性硬化症（MS）、系统性红斑狼疮（SLE）患者以及癌症相关性疲劳患者作为对照。从14种不同的EBV蛋白中合成了3054个重叠肽段，每个肽段为15聚体。通过酶联免疫吸附测定（ELISA）对选定肽段的阵列数据进行验证。通过定量聚合酶链反应（qPCR）从咽洗液样本中确定EBV血清型的患病率。
在患者和对照者中均发现了1型EBV感染。健康对照者和CFS患者之间的EBV血清阵列谱差异小于MS或SLE患者。与对照相比，我们发现CFS患者对几种含有重复序列的EBNA - 6肽段的IgG反应显著增强。EBNA - 6肽段的IgG反应与EBNA - 6蛋白反应相关性良好。EBNA - 6重复区域与多种人类蛋白显示出序列同源性。
CFS患者的EBV IgG抗体反应模式与健康对照者相当相似。在CFS患者中发现针对EBNA - 6重复序列和EBNA - 6蛋白的IgG反应增强。具有这种EBNA - 6重复序列的多种人类蛋白的同源序列可能是抗原模拟的潜在靶点。
