Yuzhong Wang

Cytoalbuminologic dissociation in Asian patients with Guillain-Barré and Miller Fisher syndromes

Cerebrospinal fluid (CSF) protein level, cell count, and its relationship to the timing of lumbar puncture were collected from patients with Guillain‐Barré syndrome (GBS) and Miller Fisher syndrome (MFS) from various Asian centers. A total of 507 patients with GBS were studied. Overall, 56% had elevated CSF protein level. This was significantly lower than that reported in a recent Dutch study (56% vs 64%). Cytoalbuminologic dissociation was also lower in the Asian cohort (55% vs 64%), with a significantly higher proportion of patients with mild pleocytosis (26% vs 15%). A lower proportion of the 164 patients with MFS had elevated CSF protein level (38% vs 56%), mild pleocytosis (11% vs 26%), and cytoalbuminologic dissociation (41% vs 55%) compared to patients with GBS. In both conditions, cytoalbuminologic dissociation was linked to the timing of lumbar puncture. Cytoalbuminologic dissociation was only observed in half of the Asian patients with GBS and MFS, and it is strongly dependent on the timing of the lumbar puncture.

Action mechanism of corticosteroids to aggravate Guillain-Barré syndrome

Corticosteroids have been proved to be ineffective for Guillain-Barré syndrome, but the mechanism remains unknown. In a rabbit model of axonal Guillain-Barré syndrome, treatment with corticosteroids significantly reduced macrophage infiltration in the spinal ventral roots and the survival rate as well as clinical improvement. On 30th day after onset, there was significantly higher frequency of axonal degeneration in the corticosteroids-treated rabbits than saline-treated rabbits. Corticosteroids may reduce the scavengers that play a crucial role for nerve regeneration, thus delay the recovery of this disease.

Silencing of miR155 Promotes the Production of Inflammatory Mediators in Guillain–Barré Syndrome In Vitro

MicroRNA-155 (miR155) has been demonstrated as a central regulator of immune responses induced by inflammatory mediators. Previous studies suggest that miR155 may play adverse effects in various diseases. We hereby explored the roles of miR155 in the pathogenesis of Guillain–Barré syndrome (GBS). Peripheral blood mononuclear cells (PBMCs) were separated from GBS patients and healthy controls. Expression of miR155 in PBMCs was detected by quantitative PCR. An inhibitor of miR155 was transfected into the cultured PBMCs and the GBS-related cytokines were detected. Significantly, our study demonstrated that miR155 was downregulated in PBMCs from GBS patients and silencing of miR155 profoundly promoted the production of Th1-type cytokines in vitro. Our data effectively demonstrate a protective role of miR155 in GBS, which suggests that miR155 may be a promising target for the therapy of the disease.

Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report

Rationale: Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterized by bilateral progressive ptosis and ophthalmoplegia. Kearns -Sayre syndrome (KSS) is a multisystem disorder with PEO, cardiac conduction block, and pigmentary retinopathy. A few individuals with CPEO have other manifestations of KSS, but do not meet all the clinical diagnosis criteria, and this is called “CPEO plus.” Patient concerns: We report a 48-year-old woman exhibiting limb weakness, ptosis, ophthalmoparesis, and cerebellar dysfunctions. Diagnoses: The patient was diagnosed as exhibiting CPEO plus syndrome. Interventions: The patient underwent clinical, genetic, histological, and histochemical analysis. She was treated orally with CoQ10, vitamin Bs, L-carnitine, and vitamin E. Outcomes: The patients serum creatine kinase levels, electrocardiography, and nerve conduction study results were normal; an electromyogram revealed myopathic findings. Magnetic resonance imaging showed global brain atrophy, particularly in the brainstem and cerebellum areas. A muscle biopsy showed the presence of abundant ragged red fibers. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed C960del mutation in 12S rRNA and homozygous mutation C2835T in 16S rRNA. She took medicines on schedule, the clinical features were similar as 2 years ago. Lessons: This is the first report of 2 rRNA mutations in a patient with MRI findings showing global brain atrophy, particularly in brainstem and cerebellum areas. Early recognition and appropriate treatment is crucial. This case highlights the cerebellar ataxia can occur in CPEO plus.

Vinpocetine Inhibited the CpG Oligodeoxynucleotide-induced Immune Response in Plasmacytoid Dendritic Cells

ABSTRACT Plasmacytoid dendritic cells (pDCs) exert dual roles in immune responses through inducing inflammation and maintaining immune tolerance. A switch of pDC phenotype from pro-inflammation to tolerance has therapeutic promise in the treatment of autoimmune diseases. Vinpocetine, a vasoactive vinca alkaloid extracted from the periwinkle plant, has recently emerged as an immunomodulatory agent. In this study, we evaluated the effect of vinpocetine on phenotype of pDCs isolated from C57BL/6 mice and explored its possible mechanism. Our data showed that vinpocetine significantly downregulated the expression of CD40, CD80, and CD86 on pDCs and increased the expression of translocator protein (TSPO), the specific receptor of vinpocetine, in pDCs. Vinpocetine significantly inhibited the Toll-like receptor 9 signaling pathway and reduced the secretion of related cytokines in pDCs through TSPO. Furthermore, viability of pDCs was significantly promoted by vinpocetine. These findings imply that vinpocetine serves as an immunomodulatory agent for pDCs and may be applied for the treatment of pDCs-related autoimmune diseases.

MicroRNA expression profiling in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory autoimmune disease affecting the peripheral nervous system. MicroRNAs (miRNAs) are a class of small noncoding RNAs that play critical roles in the process of various diseases. The miRNAs in GBS were less studied. In this study, using microarray technology, we found two miRNAs including has-miR-4717-5p and has-miR-642b-5p were upregulated in patients with GBS, which were further confirmed by PCR analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of GBS by affecting the cellular differentiation, cell survival and axonal outgrowth.

Suppressive oligodeoxynucleotides induced tolerogenic plasmacytoid dendritic cells and ameliorated the experimental autoimmune neuritis

Toll-like receptor (TLR) 9, recognizing different ligands, confers distinct features of plasmacytoid dendritic cells (pDCs). Our previous study demonstrated a role for TLR9 in the mechanism of experimental autoimmune neuritis (EAN). In this study, we explored whether suppressive oligodeoxynucleotides (sODN) could induce tolerogenic pDCs via TLR9 and thus promote the recovery of EAN. Effects of different TLR9 ligands, CpG ODN and sODN on P0 180-199 peptide-stimulated pDCs were measured by detecting the expression of co-stimulatory molecules, indoleamine 2,3-dioxygenase (IDO), secretion of Th1- and Th2-type cytokines and the TLR9 signaling pathway. CpG ODN- or sODN-treated pDCs were intravenously injected into the EAN mice and their effects were compared. Our data showed that P0180-199 peptides significantly promoted mRNA expression of co-stimulatory molecules (CD40, CD80 and CD86) in pDCs and induced secretion of Th1-type cytokines. Treatment of CpG ODN aggravated the effects of P0 180-199 peptides on pDCs; however, sODN had the opposite effects and significantly upregulated the IDO expression in pDCs. Further analysis showed that MYD88 is necessary for sODN to modulate the TLR9/NF-κB signaling in pDCs. Finally, the sODN-treated pDCs significantly promoted recovery of the EAN mice. Taken together, sODN could induce tolerogenic pDCs and thus ameliorate the EAN.

A new method of isolating spinal motor neurons from fetal mouse

BACKGROUND Isolating of primary motor neurons from animal embryos is critical for the study of neurological disease including mechanistic discovery and therapeutic development. Density gradient centrifuge taking advantage of the buoyant of motor neuron permits the enrichment of motor neurons. Despite the metrizamide, an OptiPrep medium has been introduced to separate the motor neurons by gradient centrifuge. NEW METHOD We hereby used single density gradient of OptiPrep medium to isolate the spinal motor neurons from the fetal mouse. RESULTS Single density gradient of OptiPrep medium is effective to isolate spinal motor neurons from the fetal mouse. The immunofluorescence staining analysis showed that the purity of cultured motor neurons at 72h was between 90% and 95%. COMPARISON WITH EXISTING METHOD Four gradients of OptiPrep medium have been previously used to isolate the motor neurons from spinal cord of mouse. In this study, the single gradient of OptiPrep medium was demonstrated to effectively isolate spinal motor neurons from the fetal mouse. CONCLUSIONS The single gradient of OptiPrep medium is enough to produce high purity of spinal motor neurons from the fetal mouse.

Memory B cells in Guillain-Barré syndrome

IgG autoantibodies against gangliosides show the highest titers at the disease onset of axonal Guillain-Barré syndrome (GBS), in which there are no IgM anti-ganglioside antibodies. We hypothesized that memory B cells take part in the development of producing IgG autoantibodies. In this study, we analyzed the memory B cells in patients with GBS using flow cytometry. There was significantly higher percentage of memory B cells in patients with GBS than the healthy controls. The Spearman correlation analysis demonstrated that increased percentage of memory B cells was positively correlated with the clinical severity of the patients with GBS. Our study provides the evidences that memory B cells may be involved in mechanism of GBS.

IgG-degrading enzyme of Streptococcus pyogenes (IdeS) prevents disease progression and facilitates improvement in a rabbit model of Guillain-Barré syndrome

Abstract Autoantibodies binding to peripheral nerves followed by complement deposition and membrane attack complex formation results in nerve damage in Guillain‐Barré syndrome (GBS). Strategies to remove the pathogenic autoantibodies or block the complement deposition benefit most patients with GBS. Immunoglobulin G‐degrading enzyme of Streptococcus pyogenes (IdeS) is a cysteine protease which cleaves IgG antibodies into F(ab′)2 and Fc fragments. In this study, using a rabbit model of axonal GBS, acute motor axonal neuropathy (AMAN), we demonstrated that IdeS treatment significantly reduced the disruption of Nav channels as well as activated C3 deposition at the anterior spinal root nodes of Ranvier in AMAN rabbits. IdeS significantly promoted the clinical recovery of AMAN rabbits and there were significant lower frequencies of axonal degeneration in anterior spinal roots of AMAN rabbits with IdeS treatment compared to the saline controls. Our data support that IdeS treatment is a promising therapeutic strategy for GBS. HighlightsThe therapeutic potentials of targeting degradation of IgG in AMAN were investigated.IdeS reduced the nerve damage and facilitated the clinical improvement of AMAN model.A clinical trial of IdeS may introduce an alternative therapy to current strategies of GBS.