Department of Clinical, Surgery and Experimental Medicine, University of Sassari, Sassari, Italy.
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Eur J Neurol. 2018 Aug;25(8):1076-e84. doi: 10.1111/ene.13648. Epub 2018 May 14.
Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls.
Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides.
Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su and HERV-W env-su were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF.
Increased circulating levels of Abs directed against the HERV-W env-su and HERV-W env-su peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su peptide fragment could serve as a possible early novel biomarker in patients with ALS.
人类内源性逆转录病毒(HERV)K/W 似乎在某些神经疾病(包括肌萎缩侧索硬化症,ALS)的促进和恶化中发挥作用。鉴于这些发现,研究了针对 HERV-K 和 HERV-W 包膜表面(env-su)糖蛋白抗原的血清和脑脊液(CSF)中的免疫反应,以研究 ALS、多发性硬化症(MS)和阿尔茨海默病患者以及健康对照组。
研究了分别源自 HERV-K 和 HERV-W env-su 蛋白的 4 种抗原肽,共 21 名确诊或疑似 ALS 患者、26 名可能或确诊的复发缓解型 MS 患者、18 名阿尔茨海默病患者和 39 名健康对照组。建立了间接酶联免疫吸附试验来检测针对 env-su 肽的特异性抗体(Abs)。
在所测量的针对四种不同 HERV-K 肽片段的 Abs 水平中,只有 ALS 组的 HERV-K env-su 在血清和 CSF 中均显著高于其他组。相反,在针对四种不同 HERV-W 肽片段的 Abs 水平中,只有 MS 组的血清和 CSF 中 HERV-W env-su 和 HERV-W env-su 的 Abs 水平显著升高。在 ALS 患者中,血清和 CSF 中针对 HERV-K env-su 的 Abs 水平与疾病严重程度的临床指标显著相关。
针对 HERV-W env-su 和 HERV-W env-su 肽片段的循环 Abs 水平升高可能是 MS 患者的潜在生物标志物。同样,针对 HERV-K env-su 肽片段的循环 Abs 水平升高可能是 ALS 患者的一种新的早期潜在生物标志物。