The pathogenesis of Guillain-Barre syndrome: peptidomic profiling of physiological fluids

ABSTRACT: Acute inflammatory demyelinating polyneuropathy (AIDP) - one of the forms of Guillain-Barre syndrome (GBS) - is a rare and severe disorder of the peripheral nervous system that also has an unknown etiology. One of the hallmarks of AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level in comparison with the peptidome/proteome profile of a representative number of CSF samples obtained from AIDP and multiple sclerosis (MS) patients and control patients. In total, 2355 peptide fragments related to 795 proteins were found in CSF samples from AIDP patients, 1066 peptide fragments of 253 proteins in samples from MS patients, and 774 peptide fragments of 220 proteins from control patients. Proteomic studies detected 1103 proteins in the control cohort and 1402 proteins in the AIDP cohort. Our dataset suggests that the proteome of the CSF from AIDP and control patients overlaps by as much as 67%, whereas the peptidome is only 21.5% identical. Comparison of the peptidomic and proteomic data revealed that 80% of the peptides in the CSF of AIDP patients correspond to proteins that are not present in proteomic dataset. Importantly, a considerable number of differentially represented peptides are related to the proteins involved in the arrangement of the axonal domains. The observed peptidomic dataset indicates that specific proteins, which participate in the arrangement of the myelin sheath in the nodes of Ranvier, are degraded in the course of AIDP. Here, we show that the proteins that are overrepresented in the CSF of AIDP patients are partially linked with defensive responses to bacteria and viruses. These observations are in line with the upregulation of CSF cytokines associated with innate immunity, which in turn surprisingly suggests that the destruction of axons is not accompanied by any indications of a distinct adaptive autoimmune process. We believe that the presented proteomic and peptidomic dataset of the CSF from AIDP patients will provide useful information regarding the mechanisms of AIDP pathogenesis in comparison with MS, which is the prolonged but incurable autoimmune degradation of the central nervous system.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr Georgij Arapidi 

PROVIDER: MSV000079963 | MassIVE | Wed Jul 20 16:51:00 BST 2016

SECONDARY ACCESSION(S): PXD002884

REPOSITORIES: MassIVE