Study Of Protein Biomarkers In Cerebrospinal Fluid And Serum Of Guillain-Barré Syndrome Patients

Introduction:Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory disease entity inthe peripheral nervous system (PNS). Although the exact mechanism of GBS remains largelyunknown, it is currently accepted as an organ-specific immune-mediated disorder resultingfrom a synergistic interaction between cellular and humoral immune responses toincompletely characterized antigens in the PNS. GBS consists of different clinical subtypes,including acute inflammatory demyelinating polyneuropathy (AIDP), the prototyte of GBS.The axonal variants of GBS include acute motor axonal neuropathy (AMAN), acute motorand sensory axonal neuropathy (AMSAN), the Fisher syndrome, acute pandysautonomia andacute sensory neuropathy. The etiology, immunopathogenesis and clinical features varyconsiderably among different subtypes. A laboratory hallmark of GBS is thealbumino-cytologic dissociation in the cerebrospinal fluid (CSF). Since the CSF compartmentsurrounds the proximal nerve roots, CSF serves as a potential source of biomarkers ininflammatory disorders of the spinal nerve roots, i.e. GBS. The elevated levels of CSFalbumin in GBS are known to be caused by the impaired blood-CSF barrier (B-CSF-B) at theproximal spinal nerve roots, which in turn influences the protein turnover into the CSF.Changes of CSF albumin have been studied in GBS, whereas changes in CSF levels of otherproteins are not as well documented. Although a series of studies have aimed at identificationof specific biomarkers within the CSF for diagnostic as well as prognostic evaluations ofinflammatory neuropathies such as GBS, the reliable markers are still lacking.AIDP and AMAN, an axonal variant of GBS, are the common clincal subtypes of GBS.AIDP is characterized by demyelination due to autoimmune responses against Schwann cells, whereas AMAN is caused by axonal degeneration due to aberrant autoimmune responsesagainst peripheral axons. The distinctive autoimmune targets between AIDP and AMANcould lead to release of specific proteins that may be used as biomarkers for differentiation ofAIDP and AMAN. To test this hypothesis, we determined the levels of S100B, Tau andphosphorylated neurofilament heavy protein (pNFH) in CSF and serum of GBS patients toexplore their potential for diagnostic differentiation and prognostic evaluation of the clinicalsubtypes of GBS, AIDP and AMAN.Objectives: Guillain-Barré syndrome (GBS) is an immune-mediated inflammatorydisease in the peripheral nervous system (PNS). Specific biomarkers for the clinical subtypesof GBS, acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonalneuropathy (AMAN) are still missing. The distinctive pathological features of AIDP andAMAN may lead to release of such specific biomarkers. To explore the potential of S100B,Tau and phosphorylated neurofilament heavy protein (pNFH) for diagnostic differentiationand prognostic evaluation of the clinical subtypes of GBS.Materials and methods: To explore the potentials of biochemical markers fordifferentiation and evaluation of prognosis of clinical subtypes in GBS, we used ELISA tomeasure the levels of S100B, Tau and pNFH in serum and CSF from the patients with AIDP,AMAN, viral encephalitis, and other non-inflammatory neurological disorders (OND),respectively.Results: The values of albumin quotient and IgG index in CSF are significantly higher inAIDP and AMAN than in OND. The levels of S100B, Tau and pNFH in serum and CSF areelevated in the patients with AIDP and AMAN compared to OND. The concentrations of allthese proteins are all higher in CSF than in serum. Increased levels of S100B in CSF at theacute phase are positively correlated with the GBS disability scale scores (GDSs) in AIDP,whereas enhanced levels of Tau and pNFH in CSF are positively correlated with the GDSs inAMAN.Conclusions: Increased CSF levels of S100B, Tau and pNFH at the acute phase can predict a poor prognosis and evaluate the severity of AIDP or AMAN at plateau and therecovery phase. Elevated levels of pNFH in CSF may be used for differentiating AMAN andAIDP.