Anti-Human Endogenous Retrovirus and Anti-Myelin Oligodendrocyte Glycoprotein Humoral Response in Cerebrospinal Fluid of Multiple Sclerosis Patients: A Case Control Study

Abstract

It is believed that human endogenous retrovirus (HERV)-W plays a fundamental role in multiple sclerosis (MS) pathogenesis, probably by inducing humoral and cellular immunopathological response. HERVs present regions of similarity to myelin oligodendrocyte glycoprotein (MOG) and therefore could induce autoimmunity through the mechanism of molecular mimicry via cross-humoral response. This study aimed to evaluate the impact of HERV-mediated humoral response among MS patients by assessing IgG antibody levels of HERV-W and K in cerebrospinal fluid (CSF). CSF samples were collected from MS patients (n = 25) and idiopathic intracranial hypertension (IIH) patients (n = 25). Serum samples from MS group (n = 25) were also analyzed. CSF samples were assessed for global and differential cell counts, analytical biochemistry, and oligoclonal bands analysis. ELISA was used to determine the serum and intrathecal (CSF) presence and concentration of anti-MOG, anti-HERV-W-env, and anti-HERV-K-pol antibodies. ELISA findings revealed higher concentrations of anti-MOG and HERV-W IgG in MS compared to IIH (p < 0.01 and p = 0.0142 respectively), while HERV-K IgG showed concentration to three HERV-K peptides (p < 0.01). A positive correlation was also observed between serum and CSF antibody concentration for MOG (r = 0.47 p = 0.01), HERV-W (r = 0.72 p < 0.01), and three HERV-K peptides (r = 0.49, 0.57, 0.61 and p = 0.0126, p < 0.01, and p < 0.01, respectively) among MS patients. Our findings revealed high concentrations of anti-HERV-K and -W antibodies in serum and CSF among MS patients, suggesting a possible role of humoral immunopathological response. In addition, the positive correlation between serum and CSF antibody concentration indicates the potential application of serum levels of anti-HERV and anti-MOG as biomarkers for MS.