myelin-basic-protein and Polyneuropathies

Experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN) are reproducible models of auto-allergic demyelinating diseases of central and peripheral neurons tissue respectively. EAE bears a close resemblance to naturally-occuring post-infectious encephalomyelitis and EAN to Laundry-Guillain-Barré polyneuritis, in humans. In the experimental models the antigen responsible for disease induction is a different myelin basic protein in each disease. Although a variety of humoral antibodies to various neural fractions are found in both disorders, it has been shown that disease results from cell-mediated immune reactions to specific myelin antigens.

Topics: Autoantibodies; Autoimmune Diseases; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Hypersensitivity, Delayed; Immunity, Cellular; Myelin Basic Protein; Myelin Sheath; Peripheral Nerves; Polyneuropathies

Given the availability of effective but costly treatment for acquired demyelinating neuropathies, biomarkers for these disorders are urgently needed. Here we aimed to quantify morphological abnormalities of myelinated fibers in skin biopsies from the proximal leg of patients with neuropathies to determine a potential diagnostic role of this method. We used double immunofluorescence to detect myelinated and unmyelinated fibers in thigh skin from 81 patients with polyneuropathy, 19 patients with small fiber neuropathy, and 25 controls. Dermal myelinated fibers were reduced 6.8-fold in patients with polyneuropathy (p < 0.0001). The number of dermal nerve bundles with myelinated fibers was reduced 2.7-fold (p = 0.0025). In small fiber neuropathy, myelinated fibers in dermal nerve bundles were only reduced in the length-dependent type, indicating that this subgroup may represent an early stage of generalized polyneuropathy. Elongated nodes of Ranvier were detectable in demyelinating neuropathies only. Our data suggest that changes in the number and morphology of myelinated fibers in the proximal leg can confirm the diagnosis of neuropathy, and may help to distinguish between demyelinating and axonal neuropathy, and to differentiate pure small fiber neuropathy from early polyneuropathy.

Topics: Adolescent; Adult; Aged; Biopsy; Female; Humans; Indoles; Male; Middle Aged; Myelin Basic Protein; Nerve Fibers, Myelinated; Polyneuropathies; Ranvier's Nodes; Retrospective Studies; Skin; Statistics, Nonparametric; Ubiquitin Thiolesterase; Young Adult

In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambda x, a recently described murine lambda variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine V lambda x and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient's MBP-reactive IgM/lambda using indirect ELISA procedures with MBP, a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to V lambda x as the secondary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab specific for V lambda x and, like murine mAb containing V lambda x bound human MBP but not MBP-C8 nor other common autoantigens such as DNA, thyroglobulin, or actin. The anti-MBP reactivity was selective for MBP peptide 90-170 and preferentially recognized MBP peptide 84-96. Thus, the patient's macroglobulin and perhaps certain other human Ab with a 'V lambda x idiotype' bind to MBP peptide residues 84-96, an immunodominant peptide in multiple sclerosis patients. Such binding may be involved in the pathogenesis of neural damage in patients with neuroimmunologic disorders related to plasma cell dyscrasias or autoimmunity.

Topics: Animals; Autoantibodies; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Humans; Immunodominant Epitopes; Immunoglobulin M; Macroglobulins; Multiple Sclerosis; Myelin Basic Protein; Peptide Fragments; Polyneuropathies; Rabbits; Waldenstrom Macroglobulinemia

Topics: Autoantibodies; Biopsy; Epitopes; Fluorescent Antibody Technique; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunoglobulin M; Microscopy, Confocal; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Paraproteinemias; Peripheral Nerves; Peripheral Nervous System Diseases; Polyneuropathies; S100 Proteins; Sural Nerve

Encephalitis and polyneuritis occurring after rabies vaccination are believed to be immunologically mediated. We studied antibody responses to neural antigens in 36 patients with major neurologic complications, 25 with minor complications, and 39 with no complications after immunization with a brain-derived, Semple rabies vaccine. Patients with major complications had significantly elevated levels of antibody to brain white matter as compared with the other groups (P less than 0.001). Assays for antibody to selected central nervous system antigens showed that high levels of serum and cerebrospinal fluid antibody to myelin basic protein correlated with the presence of major neurologic complications (both central and peripheral nervous systems). The level of antibody to cerebroside correlated best with the number of injections of vaccine, but like antibody to myelin basic protein, the antibody to cerebroside was present in the cerebrospinal fluid of patients with major complications. Some patients with major complications also had antibodies directed to the gangliosides GD1b and GT1b. No antibodies to myelin-associated glycoprotein were detected in any of the samples. These data implicate myelin basic protein as an encephalitogen in these autoimmune diseases of the human nervous system, but suggest that immune responses to cerebroside and certain gangliosides may have an augmentative role in severe disease.

Topics: Autoantibodies; Brain; Cerebrosides; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Humans; Myelin Basic Protein; Peripheral Nerves; Polyneuropathies; Rabies Vaccines; Time Factors; Vaccination

Topics: Encephalomyelitis, Autoimmune, Experimental; Humans; Myelin Basic Protein; Polyneuropathies; Rabies Vaccines

Sera of 23 patients with Waldenström's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenström sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenström's macroglobulinaemia.

Topics: Aged; Antibody-Dependent Cell Cytotoxicity; Complement Fixation Tests; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Middle Aged; Myelin Basic Protein; Myelin Sheath; Peripheral Nerves; Polyneuropathies; Waldenstrom Macroglobulinemia

Polyneuropathies are diffuse diseases of the peripheral nervous system. Pathological and anatomical investigations of the nerve fibres show that alterations of the peripheral axon and myelin are most significant at the distal end of the nerve fibres. Alcoholic polyneuropathy primarily affects the axon; during the chronic course of the disease, however, the myelin sheath is involved into the pathological process. Polyneuropathies are characterized by a deficiency and metabolic disturbance of the vitamins B1, B6 and B12. The vitamins of the B-group not only play an important role in the intermediate metabolism, but in paticular pathological situations high concentrations of the vitamins are necessary at a cellular and subcellular level. The experimental allergic neuritis (EAN) may be considered as a model of polyneuropathies characterized by disturbances of myelin metabolism. EAN was induced by the injection of human peripheral nerve homogenate the complete Freund's adjuvants. During EAN a marked reduction of phosphatidylinositol, sulfatides and serine-plasmalogen as well as a significant increase of phospholipase A2 activity could be observed.

Topics: Alcoholism; Animals; Avitaminosis; Axons; Diabetic Neuropathies; Humans; Lipid Metabolism; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Neuritis, Autoimmune, Experimental; Polyneuropathies; Polyradiculoneuropathy; Rabbits