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体液免疫对人类内源性逆转录病毒 K/W 的反应可区分肌萎缩侧索硬化症和其他神经疾病。

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

机构信息

Department of Clinical, Surgery and Experimental Medicine, University of Sassari, Sassari, Italy.

Department of Biomedical Sciences, University of Sassari, Sassari, Italy.

出版信息

Eur J Neurol. 2018 Aug;25(8):1076-e84. doi: 10.1111/ene.13648. Epub 2018 May 14.

Abstract

BACKGROUND AND PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景与目的

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。

方法

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)。

结果

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。

结论

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。

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