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Peripheral Nerve Myelin (peripheral + nerve_myelin)
Selected AbstractsMYELIN PROTEIN P-0-SPECIFIC IGM PRODUCING MONOCLONAL B CELL LINES WERE ESTABLISHED FROM POLYNEUROPATHY PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002M Kvarnstrom Monoclonal expansion of B cells and plasma cells, producing antibodies against ,self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenstroms'macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P-0, using beads coated with P-0. P-0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P-0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5(+) positive, although the expression declined in vitro over time. The anti-P-0 antibodies were of IgM-lambda type. The antibodies belonged to the V(H)3 gene family with presence of somatic mutations. The IgM reacted with P-0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5(+) clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P-0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation. [source] Novel MPZ Mutation In A Sporadic CMT PatientJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001E Bellone Mutations in the gene for the major structural protein component of peripheral nerve myelin, myelin protein zero (MPZ), are associated with some forms of hereditary neuropathies such as Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). The common pathological characteristics of these allelic disorders are severe demyelination and remyelination of peripheral nerves. Recently, MPZ mutations were also found in patients with the axonal form of CMT neuropathy (CMT2). We studied a patient with negative familiar history and clinical and electrophysiological features of Charcot-Marie-Tooth disease: distal muscle weakness and atrophy, foot deformities (pes cavus), and severely reduced nerve conduction velocities in the motor and sensory nerves. The sural nerve biopsy showed marked loss of myelinated fibers, few onion bulbs, and a high percentage of fibers showing excessive myelin outfoldings. DNA analysis excluded CMT1A duplication by Southern blot and by pulsed field gel electrophoresis methods. SSCP analysis of all six exons of MPZ revealed a shift band in exon 2 in the patient's DNA. No such difference was detected in normal controls. Direct sequencing disclosed a G , A transition at nucleotide position 181. This base substitution predicts the replacement of aspartic acid with asparagine at codon 61. A mutation at the same codon (but different amino acid replacement) was recently identified in a family with the axonal type of CMT, in which the disease was autosomal dominantly inherited. This finding provides further confirmation of the role of MPZ gene in peripheral neuropathies and suggests that MPZ coding region mutations may account for a considerable number of CMT cases which do not involve DNA duplication on 17p11.2-p12. This research was partially supported by a MURST and an Ateneo grant to FA, by a Ministero della Sanità grant to PM. Our laboratory is a member of the European Charcot-Marie-Tooth Consortium co-ordinated by Prof. Christine Van Broeckhoven. [source] Role Of Campylobacter Jejuni In Experimental Allergic Neuritis: A Morphological And Biochemical StudyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001M Laura Objective: The aim of the study was to evaluate if Campylobacter jejuni (C.j.) when used as an adjuvant would be able to produce a different form of Experimental Allergic Neuritis (EAN). We present here some preliminary results. Background: EAN is considered the in vivo model of Guillain-Barrè Syndrome (GBS), which is often preceded by c.j. infection. EAN can be induced in Lewis rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), an emulsion formed by oil-in-water and dead mycobacteria. An adjuvant is usually necessary for the induction of EAN because it enhances the immunogenicity of the antigen. Clinically EAN is characterized by an acute monophasic course and progressive tail and limb weakness. The pathological finding is represented by marked demyelination affecting the roots and the sciatic nerve. Methods: 4 Lewis rats were immunized with an emulsion containing 2 mg of bovine peripheral myelin and C.j. strain Penner 0:41 in incomplete Freund's adjuvant (IFA). They were compared to 4 controls immunized with the same amount of peripheral myelin in CFA. The clinical course of the disease and the histological pattern of the roots and the sciatic nerve were examined. Anti-peripheral myelin, anti-C.jejuni and anti-GM1 antibodies' reactivity was detected by an ELISA assay. A biochemical study was performed to test the role of cell- and humoral-mediated responses. Results: The Lewis rats immunized with the C.j. as an adjuvant showed a delayed onset and a milder course of disease. Pathology in the roots was characterized by predominant demyelination, whereas the sciatic nerve presented very little signs of damage. Conclusion: This serotype of C.j. appears to be a less effective adjuvant in inducing EAN rather than Mycobacteria. Further studies are necessary to elucidate the pathogenetic mechanisms involved in GBS. [source] The Critical Role of IL-12p40 in Initiating, Enhancing, and Perpetuating Pathogenic Events in Murine Experimental Autoimmune NeuritisBRAIN PATHOLOGY, Issue 4 2002Lei Bao Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL-12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T-cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain-Barré syndrome of humans. Here, EAN was established in IL-12 p40 deficient mutant (IL-12 -/- ) C57BL/6 mice by immunization with P0 peptide 180,199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. In these IL-12 -/- mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild-type mice. The former group's clinical manifestations were associated with less P0-peptide 180,199 induced secretion of interferon-, (IFN-,) by splenocytes in vitro and low production of anti-P0-peptide 180,199 IgG2b antibodies in serum. Fewer IFN-, and TNF-, producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12 -/- mice, consistent with impaired Th1 functions and response. However, the IL-12 deficiency appeared not to affect P0 peptide 180,199-specific T-cell proliferation. These results indicate that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. This information augments consideration of IL-12 as a therapeutic target in Guillain-Barré syndrome and other T-cell-mediated autoimmune diseases. [source] Multifocal motor neuropathy caused by a B-cell lymphoma producing a monoclonal IgM autoantibody against peripheral nerve myelin glycolipids GM1 and GD1bBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Masaaki Noguchi Summary., Various data support the pathogenetic significance of serum IgM autoantibodies against glycolipid GM1 in patients with multifocal motor neuropathy. Although some patients with this neuropathy have an extraneural lymphoma, IgM anti-GM1 glycolipid autoantibodies have not been investigated in these cases. We found IgM anti-GM1 autoantibody in the serum of a 52-year-old man who developed multifocal motor neuropathy that was associated with an extraneural diffuse large B-cell lymphoma. An autopsy showed severe widespread demyelination without lymphoma cell infiltration in the peripheral nerves. Immunofluorescent flow cytometry and thin-layer chromatographic immunostaining demonstrated that most of the anti-GM1 antibody in the serum was monoclonal IgM of , type, which was also demonstrable in secretory form on lymphoma cells. The antibody showed affinity for the Gal,1-3GalNAc terminal disaccharide of glycolipids GM1 and GD1b, which both are widespread in peripheral nerve myelin. Enzyme-linked immunosorbent assay demonstrated that this antibody was much more abundant in lymphoma cell culture supernatant than in normal lymphocyte culture supernatant. Thus, our patient's B-cell lymphoma cells produced a monoclonal IgM , autoantibody against this terminal disaccharide residue. This antibody bound to glycolipids GM1 and GD1b in peripheral motor nerve myelin, presumably initiating formation of destructive immune complexes that caused multifocal motor neuropathy. [source] | ||||||||||