Humoral immunity response to HERV-K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases

BACKGROUND AND PURPOSE: Human endogenous retroviruses-K/W seem play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) of ALS, multiple sclerosis (MS) and Alzheimer's disease (AD) patients, and in healthy controls (HCs). METHODS: Four antigenic peptides derived respectively from HERV-K and HERV-W env surface proteins were studied in twenty-one definite or probable ALS, twenty-six possible or definite relapsing-remitting (RR) MS, eighteen patients with AD and thirty-nine HCs. An indirect ELISA was set up to detect specific antibodies (Abs) against env surface peptides. RESULTS: Among the measured levels of Abs against the four different HERV-K peptide fragments, HERV-K env-su 19-37 only was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, among the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in serum and CSF of MS, compared to other groups. In ALS patients, the HERV-K env-su 19-37 antibodies 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 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su19-37 peptide fragment could serve as possible early novel biomarker in patients with ALS. This article is protected by copyright. All rights reserved.