Abstract
Local synthesis of antibodies and presence of oligoclonal bands in the cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS). We investigated the frequency of antibodies against mycobacterial and relevant human epitopes in the CSF of patients with MS or neuromyelitis optica spectrum disorder (NMOSD) and whether these antibodies differed from those present in the serum. Matched serum and CSF samples from 46 patients with MS, 42 patients with NMOSD, and 29 age-matched and sex-matched control subjects were screened retrospectively for the presence of antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) pentapeptide (MAP_5p), MAP_2694295–303, and myelin basic protein (MBP)85–98 peptides by using indirect ELISA. Serum levels of anti-MAP_5p and anti-MAP_2694295–303 antibodies were highly prevalent in patients with MS when compared to patients with NMOSD and controls. Several patients with MS had detectable anti-MAP_5p and anti-MAP_2694295–303 antibodies in the CSF. Furthermore, a group of patients with MS showed intrathecally restricted production of antibodies against these peptides. Women appeared to mount a stronger humoral response to mycobacterial peptides than men. No significant difference in the frequency of anti-MBP85–98 antibodies was found between patients with MS and those with NMOSD. These data highlight the zoonotic potential of MAP, which suggests its involvement in MS etiopathogenesis.
Highlights
T cells directly mediate inflammatory damage within the central nervous system (CNS) in multiple sclerosis (MS), emerging evidence has highlighted a crucial role of B cells as precursors of antibody-secreting plasma cells and as antigen-presenting cells for T-cell activation [1]
Very few antibodies in the serum and cerebrospinal fluid (CSF) samples reacted with the MBP85–98 peptide and the difference between MS and neuromyelitis optica spectrum disorder (NMOSD) groups was not significant
Our findings are in line with those obtained recently by Mameli et al who observed an intrathecal specific synthesis (AI > 1.5) of immunoglobulin G (IgG) against various Mycobacterium avium subspecies paratuberculosis (MAP) peptides in Italian patients with MS [5]
Summary
T cells directly mediate inflammatory damage within the central nervous system (CNS) in multiple sclerosis (MS), emerging evidence has highlighted a crucial role of B cells as precursors of antibody-secreting plasma cells and as antigen-presenting cells for T-cell activation [1]. Increased immunoglobulin G (IgG) intrathecal synthesis in the CNS is considered a hallmark of clinically defined MS [3]. Both elevated IgG index and oligoclonal bands (OCBs) are detectable in more than 90% of patients with MS [3]. The study of intrathecal synthesis is a quantitative and sensitive method for determining the presence of specific antibodies in the CNS and the Antibody Index (AI) is calculated to detect brain-derived microorganism-specific antibodies in the CSF [4]. Antibodies against different Mycobacterium avium subspecies paratuberculosis (MAP), Epstein–Barr virus (EBV), and human homologue peptides including myelin basic protein (MBP) have been detected in the cerebrospinal fluid (CSF) of Italian patients with MS during the relapse phase [5], which indicates a role of the bacterium or virus in enhancing inflammation through a molecular mimicry mechanism [6]
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