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

Background and purposeHuman 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. MethodsFour 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. ResultsAmongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su(19-37) 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(93-108) and HERV-W env-su(248-262) were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su(19-37) Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. ConclusionsIncreased 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-su(19-37) peptide fragment could serve as a possible early novel biomarker in patients with ALS.