Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides.
Michael GranerTiffany PointonSean MantonMiyoko GreenKathryn DennisonMollie DavisGino BraiottaJulia CraftTaylor EdwardsBailey PolonskyAnthony FringuelloTimothy VollmerXiaoli YuPublished in: PloS one (2020)
IgG oligoclonal bands (OCBs) are present in the cerebrospinal fluid (CSF) of more than 95% of patients with multiple sclerosis (MS), and are considered to be the immunological hallmark of disease. However, the target specificities of the IgG in MS OCBs have remained undiscovered. Nevertheless, evidence that OCBs are associated with increased levels of disease activity and disability support their probable pathological role in MS. We investigated the antigen specificity of individual MS CSF IgG from 20 OCB-positive patients and identified 40 unique peptides by panning phage-displayed random peptide libraries. Utilizing our unique techniques of phage-mediated real-time Immuno-PCR and phage-probed isoelectric focusing immunoblots, we demonstrated that these peptides were targeted by intrathecal oligoclonal IgG antibodies of IgG1 and IgG3 subclasses. In addition, we showed that these peptides represent epitopes sharing sequence homologies with proteins of viral origin, and proteins involved in cell stress, apoptosis, and inflammatory processes. Although homologous peptides were found within individual patients, no shared peptide sequences were found among any of the 42 MS and 13 inflammatory CSF control specimens. The distinct sets of oligoclonal IgG-reactive peptides identified by individual MS CSF suggest that the elevated intrathecal antibodies may target patient-specific antigens.
Keyphrases
- multiple sclerosis
- mass spectrometry
- ms ms
- end stage renal disease
- cerebrospinal fluid
- disease activity
- amino acid
- ejection fraction
- chronic kidney disease
- newly diagnosed
- rheumatoid arthritis
- peritoneal dialysis
- oxidative stress
- pseudomonas aeruginosa
- prognostic factors
- systemic lupus erythematosus
- dna damage
- healthcare
- dna repair
- cell proliferation
- stem cells
- dendritic cells
- signaling pathway
- social media
- ankylosing spondylitis
- patient reported outcomes
- cystic fibrosis
- cell death
- high speed
- genetic diversity
- neural network