Neural cell adhesion molecule 1 is a cellular target engaged plasma biomarker in demyelinating Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Elevated plasma concentrations of neural cell adhesion molecule 1 (NCAM1) and p75 neurotrophin receptor (p75) in patients with peripheral neuropathy have been reported. This study aimed to determine the specificity of plasma concentration elevation of either NCAM1 or p75 in a subtype of Charcot-Marie-Tooth disease (CMT) and its correlation with pathologic nerve status and disease severity. METHODS: Blood samples were collected from 138 patients with inherited peripheral neuropathy and 51 healthy controls. Disease severity was measured using Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNSv2), and plasma concentrations of NCAM1 and p75 were analyzed by enzyme-linked immunosorbent assay. Eight sural nerves from CMT patients were examined to determine the relation of histopathology and plasma NCAM1 levels. RESULTS: Plasma concentration of NCAM1, but not p75, was specifically increased in demyelinating subtypes of CMT (median = 7100 pg/mL, p < 0.001), including CMT1A, but not in axonal subtype (5964 pg/mL, p > 0.05), compared to the control (3859 pg/mL). CMT1A patients with mild or moderate severity (CMTNSv2 < 20) showed higher levels of plasma NCAM1 than healthy controls. Immunofluorescent NCAM1 staining for the sural nerves of CMT patients showed that NCAM1-positive onion bulb cells and possible demyelinating Schwann cells might be associated with the specific increase of plasma NCAM1 in demyelinating CMT. CONCLUSIONS: The plasma NCAM1 levels in demyelinating CMT might be a surrogate biomarker reflecting pathological Schwann cell status and disease progression.

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot-Marie-Tooth disease type 1A.

Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot-Marie-Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r = - 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology.

Serum CXCL13 reflects local B-cell mediated inflammatory demyelinating peripheral neuropathy.

Immune damages on the peripheral myelin sheath under pro-inflammatory milieu result in primary demyelination in inflammatory demyelinating neuropathy. Inflammatory cytokines implicating in the pathogenesis of inflammatory demyelinating neuropathy have been used for the development of potential biomarkers for the diagnosis of the diseases. In this study, we have found that macrophages, which induce demyelination, expressed a B-cell-recruiting factor CXC chemokine ligand 13 (CXCL13) in mouse and human inflammatory demyelinating nerves. The serum levels of CXCL13 were also higher in inflammatory demyelinating neuropathic patients but not in acute motor axonal neuropathy or a hereditary demyelinating neuropathy, Charcot-Marie-Tooth disease type 1a. In addition, CXCL13-expressing macrophages were not observed in the sciatic nerves after axonal injury, which causes the activation of innate immunity and Wallerian demyelination. Our findings indicate that the detection of serum CXCL13 will be useful to specifically recognize inflammatory demyelinating neuropathies in human.

Metal plasma immersion ion implantation and deposition (MePIIID) on screw-shaped titanium implant: The effects of ion source, ion dose and acceleration voltage on surface chemistry and morphology.

The present study investigated the effect of metal plasma immersion ion implantation and deposition (MePIIID) process parameters, i.e., plasma sources of magnesium and calcium, ion dose, and acceleration voltage on the surface chemistry and morphology of screw-type titanium implants that have been most widely used for osseointegrated implants. It is found that irrespective of plasma ion source, surface topography and roughness showed no differences at the nanometer level; that atom concentrations increased with ion dose but decreased with acceleration voltage. Data obtained from X-ray photoelectron spectroscopy and auger electron spectroscopy suggested that MePIIID process produces 'intermixed' layer of cathodic arc deposition and plasma immersion ion implantation. The MePIIID process may create desired bioactive surface chemistry of dental and orthopaedic implants by tailoring ion and plasma sources and thus enable investigations of the effect of the surface chemistry on bone response.