Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0152025 (polyneuropathy)
 7,862 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear.
 ...
PMID:Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I). 128 71

A human monoclonal IgM lambda antibody, directed against MAG, obtained from a patient with polyneuropathy associated with a gammopathy, was used as an immunogen to generate mouse monoclonal anti-idiotype antibodies. One hybridoma antibody, designated A8F2, reacts uniquely with the M-IgM of the patient, shows high affinity binding to the patient's M-IgM, and dose-dependently inhibits binding of the patient's M-IgM to its specific antigen MAG. Thus, A8F2 is a monoclonal anti-idiotype antibody that recognizes a region of the MAG binding site of the patient's IgM. Use of this anti-idiotype antibody in a competition RIA revealed the presence of naturally occurring anti-idiotype in the patient's serum. Because anti-idiotype antibodies may be part of a mechanism for down-regulation of antibody production, the use of A8F2 to induce a specific immunosuppression should be considered.
 ...
PMID:A monoclonal anti-idiotypic antibody against a human monoclonal IgM with specificity for myelin-associated glycoprotein. 258 12

Attention has recently been directed toward patients having a polyneuropathy and a monoclonal IgM anti-myelin-associated glycoprotein (anti-MAG) antibody. The possibility of a pathogenetic role for the anti-MAG antibody in the evolution of the polyneuropathy and in the development of central nervous system signs, including tremor and ataxia, remains unresolved. In 5 patients with this syndrome whose clinical courses were followed closely, in 1 of whom a complete postmortem examination of the nervous system was performed, we made the following observations: the anti-MAG antibody did not localize to the compact layer of the myelin sheath in affected nerves, but did localize to areas of myelin splitting; anti-MAG antibody present in the sural nerve of an affected individual for 7 years was not associated with progressive pathology; anti-MAG antibody was not deposited in the central nervous system of an affected individual, although the antibody did bind to these same tissues in vitro; deposition of anti-MAG antibody observed at postmortem examination did not correlate with the degree of pathological change; and study of the peripheral nervous system favored a primary axonal neuropathy with secondary demyelination.
 ...
PMID:Polyneuropathy and IgM monoclonal gammopathy: studies on the pathogenetic role of anti-myelin-associated glycoprotein antibody. 258 96

A number of confounding factors can be identified from the search for autoimmune mechanisms over the last 2 decades that may be relevant for future studies. (1) An apparently homogeneous clinical disorder may represent more than one disease process and thereby imply antibody/antigen heterogeneity as, for example, in MG with and without detectable anti-AChR antibodies. In some cases, physiologic studies allow the different forms of the disease to be distinguished as in AIDP and acute inflammatory axonal polyneuropathy. (2) A homogeneous disorder (e.g., LEMS) may have at least two different triggering mechanisms (SCLC and an unknown stimulus). (3) Antigen density may be too low to be detected by the immunohistologic techniques available, as initially occurred in MG and LEMS. (4) Autoantibodies may be detected that are irrelevant to the primary disease, such as anti-striated muscle antibodies in MG. (5) Poor antibody cross-reactivity between species may mean that the pathogenic antibody is undetected in binding assays or in experimental passive transfer studies. For example, anti-AChR antibody in MG shows less than 5% reactivity with Torpedo AChR. (6) A poor regenerative capacity of the target antigen may mean that reduction of circulating autoantibodies by either plasma exchange or ISD treatment is not associated with detectable clinical improvement, as may be the case in SSN in which DRG cells appear to be the target. TABLE 5 summarizes the extent to which the data reviewed have established a role for pathogenic antibodies in the light of the postulates for autoimmunity set out earlier and ranks the disorders accordingly. Only in MG with detectable anti-AChR antibody are all the postulates met, including definition of the antigen, experimental passive transfer by the IgG fraction of MG sera, active immunization of experimental animals, and propagation. In both LEMS and the IgM kappa anti-MAG demyelinating neuropathy the antigen is known, although better characterized in LEMS; the epitopes are not yet defined in either. Data relating to passive transfer are more extensive in LEMS, however; systemic passive transfer of anti-MAG has not yet been reported. In neither condition is an animal model available. In the demyelinating neuropathies, the case for autoimmunity is less complete. Neither in AIDP nor in CIDP is the antigen known, and thus the relevance of the different EAN disorders is uncertain. Current evidence thus rests on the demonstration of serum IgM antibodies that react with peripheral nerve myelin and fix complement and on the intraneural passive transfer studies.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Autoimmunity in neuromuscular disease. 284 91

We measured residual latency (RL), motor conduction velocity (MCV), and terminal latency index (TLI) in 15 patients with neuropathy and anti-MAG or SGPG antibodies and compared these to values obtained in 103 patients with other types of polyneuropathy (PN) and to 57 normal subjects. Ten patients had anti-MAG antibody titers of 25,600 or higher, and 5 had titers between 800 and 12,600. Patients with the highest titers had longer RL, slower MCV and shorter TLI than those with lower titers, acute or chronic inflammatory demyelinating PN, hereditary neuropathy, and metabolic or axonal neuropathy. In contrast F-wave latencies did not contribute to the differentiation between the groups of demyelinating neuropathies. RL and TLI correlated best with anti-MAG antibody titers, whereas there was a poor correlation with anti-SGPG titers suggesting that MAG more than SGPG may be the antigen in PN, and that the distal nerves are affected more than their proximal segments. The RL rather than TLI turned out to be the best variable to classify the demyelinating type of anti-MAG neuropathy. Sural nerve biopsy in 5 of the patients with the highest titer of anti-MAG antibodies showed deposits of IgM and C3 on the myelin sheaths, pronounced demyelination and widening of the myelin lamellae. In 4 of the patients with lower titers demyelination was absent or less pronounced.
 ...
PMID:Motor conduction parameters in neuropathies associated with anti-MAG antibodies and other types of demyelinating and axonal neuropathies. 754 Feb 58

A 56-year-old man gradually developed paresthesia and muscular weakness of the left hand and feet for two years. On admission, neurological examination showed predominantly sensory polyneuropathy. Electrophysiological study and sural nerve biopsy demonstrated segmental demyelination, but any underlying congenital, toxic, metabolic or neoplastic cause was failed to reveal. The serum IgM level was 576 mg/dl, while IgG and IgA were normal. An immunoblot analysis and ELISA showed serum IgM antibody that reacted with human MAG. Serum IgM M-protein, however, was detectable not by conventional serum protein electrophoresis and immunoelectrophoresis, but by immunofixation. Anti-MAG antibodies should be evaluated in the patients with slowly progressive demyelinating polyneuropathy of unknown etiology, even if no serum M-protein is detected by conventional methods. Serum M-protein may play a role of pathogenesis of demyelination, and immunofixation method could be beneficial to detect small amount of M-protein.
 ...
PMID:[Polyneuropathy with IgM-antibody to myelin-associated glycoprotein without detectable M-protein by conventional analysis--report of a case]. 768 55

A 64 year old woman with monoclonal IgM Kappa cryoglobulinemia had developed neurologic, vascular and bone involvements. If each features were previously reported, their association appears to be rare. The polyneuropathy was consistent with an IgM anti MAG neuropathy rather than a cryoglobulinemic neuropathy. The vascular occlusion is well known in dysglobulinemia. The diffuse osteosclerosis without medullary fibrosis or myeloproliferative disorder was as like as a Schnitzler's syndrome (chronic urticaria, osteosclerosis, monoclonal IgM Kappa gammopathy.
 ...
PMID:[Multiple complications of monoclonal IgM]. 793 61

The spectrum of peripheral neuropathy associated with monoclonal gammapathy is wide: peripheral neuropathy associated with IgM monoclonal gammapathy, in which serum antibody activity has been demonstrated against MAG (myelin-associated-glycoprotein) and SGPG, mainly presents as a chronic demyelinating sensory polyneuropathy, with predominant tremor and ataxia. Polyneuropathy reported in association with multiple myeloma or MGUS (monoclonal gammapathy of undetermined significance) IgG and IgA are more heterogenous: mainly axonal, mixed or sometimes demyelinating as in POEMS syndrome. The treatment of these polyneuropathies is evaluated in trials in progression using corticosteroids, plasma exchanges and IgIV (polyvalent immunoglobulins).
 ...
PMID:[Neurological manifestations of monoclonal gammopathies]. 838 55

Eleven patients with demyelinating polyneuropathy associated with monoclonal IgM antibodies were randomized to receive IVIg or placebo, monthly, for 3 months in a double-blind study. After a washout period, they crossed over to the alternate therapy. Response was gauged by evaluating muscle strength, sensation, and neuromuscular symptoms at baseline, after 3 months, and at treatment's end. After IVIg therapy, the strength improved in only 2 of 11 patients, by 28 and 38.5 points from baseline, and declined after placebo. In 1 other patient, the sensory score improved by 13 points. Antibody titers to MAG/SGPG or gangliosides did not appreciably change. We conclude that IVIg has only a modest benefit to not more than 18% of patients with IgM paraproteinemic demyelinating neuropathy.
 ...
PMID:A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy. 895 21

Forty cases of polyneuropathy associated with IgM monoclonal gammopathy were retrospectively studied to investigate the relevance of clinical and electrophysiological features to M-protein antibody activity. There were 26 men and 14 women; mean age was 65 +/- 11.7 years at the time of the study. Thirty-nine patients had a symmetrical polyneuropathy, of whom 13 had a predominantly sensory and 17 a purely sensory neuropathy (i.e., 30 sensory neuropathies). The remaining patient had a multifocal mononeuropathy. Electrophysiological studies allowed the polyneuropathies to be classified as demyelinating in 33 cases (82.5%) and axonal in 6 cases. Antibody studies disclosed anti-MAG antibodies in 65% and anti-SGPG antibodies in 82.5% of patients. Anti-MAG antibodies were associated with only demyelinating polyneuropathies. Anti-SGPG antibodies were found in 91% of demyelinating polyneuropathies and 50% of axonopathies. In addition, anti-MAG/SGPG antibody activity was significantly correlated with the subgroup of sensory neuropathies (P < 0.01). Last, antisulfatide antibodies were found at significant titers in 18 cases, and their presence was significantly correlated with anti-MAG/SGPG antibody activity, but not with some clinical/electrophysiological features.
 ...
PMID:Peripheral neuropathy associated with IgM monoclonal gammopathy: correlations between M-protein antibody activity and clinical/electrophysiological features in 40 cases. 942 24


1 2 3 4 5 6 Next >>