RESUMO
BACKGROUND AND PURPOSE: In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. METHODS: We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. RESULTS: A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%-50.9%) than in the placebo group (21.1%-25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. CONCLUSIONS: Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.
Assuntos
Avaliação da Deficiência , Força da Mão/fisiologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Método Duplo-Cego , HumanosRESUMO
Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.
Assuntos
Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Síndrome de Guillain-Barré/tratamento farmacológico , Humanos , Miosite/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológicoRESUMO
BACKGROUND: Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten-free diet. METHODS: Case series. RESULTS: We report three patients with biopsy-proven CD who developed cerebellar ataxia and neuropathic pain despite strict adherence to a gluten-free diet. A small fiber neuropathy was suggested by skin biopsy findings in two patients. All patients' symptoms, including small fiber neuropathy symptoms, responded to treatment with intravenous immunoglobulin (IVIG). Discontinuation of IVIG in two patients resulted in worsened ataxia that reversed after resumption of IVIG. CONCLUSION: Intravenous immunoglobulin may be effective in treating cerebellar ataxia and small fiber neuropathy associated with CD, suggesting an immune pathogenesis. Further prospective, controlled studies are necessary to determine the long-term response to IVIG or other immunomodulation therapy.
Assuntos
Doença Celíaca/complicações , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/imunologia , Adulto , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/imunologia , Vias Aferentes/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Cerebelo/efeitos dos fármacos , Cerebelo/imunologia , Cerebelo/fisiopatologia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Fibras Nervosas Amielínicas/efeitos dos fármacos , Fibras Nervosas Amielínicas/imunologia , Fibras Nervosas Amielínicas/patologia , Nociceptores/efeitos dos fármacos , Nociceptores/imunologia , Nociceptores/patologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/imunologia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Tratos Espinocerebelares/efeitos dos fármacos , Tratos Espinocerebelares/imunologia , Tratos Espinocerebelares/fisiopatologia , Resultado do TratamentoRESUMO
Patients with anti-myelin associated glycoprotein (anti-MAG) neuropathy have uniform slowing without temporal dispersion, but do usually have disproportionately distal slowing. We evaluated distal compound muscle action potential (CMAP) dispersion in 29 patients with anti-MAG/sulphated glucuronyl paragloboside (SGPG) neuropathy (titres > or = 12,800). Among 138 motor responses, 15% (tibial), 7.3% (peroneal), 10.7% (median) and 13.8% (ulnar) had distal CMAP duration > 9 ms. Disproportionate distal slowing with normal distal CMAP duration in the arms may be useful to differentiate chronic inflammatory demyelinating polyneuropathy from anti-MAG/SGPG associated neuropathy.
Assuntos
Potenciais de Ação , Músculo Esquelético/fisiopatologia , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/fisiopatologia , Anticorpos , Braço/fisiologia , Eletrofisiologia , Feminino , Globosídeos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/imunologia , Estudos RetrospectivosRESUMO
Peripheral neuropathy (PN) in inflammatory bowel disease (IBD) patients has been reported as individual cases or small series; however, its clinical and electrodiagnostic features have not been well characterized. We conducted a retrospective review of patients with PN and either Crohn's disease (CD) or ulcerative colitis (UC). Eighteen patients with CD and 15 patients with UC were identified after other PN causes were excluded. Male predominance and mean age of PN presentation in the fifties was seen in both groups. Demyelinating neuropathy (CIDP or MMN) occurred in close to 30% of the patients, in a higher percentage of women, than in the non-demyelinating patients. One-third of CD and UC patients had small-fibre or large-fibre sensory axonal PN, while approximately 40% of the CD and UC patients had large-fibre axonal sensorimotor PN. PN symptoms began earlier in the course of CD than in UC (P < 0.05). Patients with large-fibre axonal PN were older than patients with small-fibre sensory axonal PN (P < 0.05). Close to 60% of each group received immunotherapy with different agents. Half of those treated with CD and 40% with UC had demyelinating PN. Most of the patients who completed immunotherapy in both groups improved; all the patients with demyelinating neuropathy had either moderate or major improvement. The PN syndromes in IBD patients are diverse. Demyelinating forms may occur at any time, but early in the IBD course, pure sensory neuropathy is more common. Response to immunotherapy may occur in both demyelinating and axonal neuropathies.
Assuntos
Doenças Inflamatórias Intestinais/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Fatores Etários , Idoso , Colite Ulcerativa/complicações , Colite Ulcerativa/terapia , Doença de Crohn/complicações , Doença de Crohn/terapia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/terapia , Feminino , Humanos , Imunoterapia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Doenças do Sistema Nervoso Periférico/patologia , Estudos Retrospectivos , Fatores Sexuais , Resultado do TratamentoRESUMO
BACKGROUND: Postmortem studies of the subiculum from subjects with schizophrenia have detected smaller pyramidal cell bodies and diminished immunoreactivity for the dendritic protein, microtubule-associated protein 2. While these findings suggest that subicular pyramidal cell dendrites may be structurally altered in subjects with schizophrenia, this possibility had not been tested directly. METHODS: Rapid Golgi impregnation of archival brain specimens was used to compare the morphologic characteristics of subicular dendrites in subjects with schizophrenia (n = 13) and mood disorders (n = 6) with subjects without psychiatric disease (n = 8). The specimens were processed and analyzed by physicians blind to diagnosis. The extent of dendritic trees in the subiculum and fusiform gyrus was examined by Sholl analysis. Spine density on apical dendrites of subicular pyramidal cells was determined at a fixed distance from the cell body. RESULTS: Spine density and arborization of subicular apical dendrites were significantly related to diagnostic group. Spine density was significantly lower in the schizophrenia and mood disorder groups than in the nonpsychiatric group. Among the mood disorder cases, diminished spine density was apparently related to a strong family history of major psychiatric diseases. There were no significant effects of diagnostic group on Sholl analysis of nonapical subicular dendrites nor on Sholl analysis of dendrites of neocortical pyramidal cells in the fusiform gyrus. CONCLUSIONS: We have observed an association between schizophrenia and major mood disorders and structural abnormalities of subicular apical dendrites. Further studies are needed to test this association in a larger sample and to evaluate the potential role of family history and of confounding factors, such as medications and chronic institutionalization.
Assuntos
Dendritos/patologia , Hipocampo/patologia , Transtornos do Humor/patologia , Esquizofrenia/patologia , Adulto , Idoso , Corantes , Dendritos/fisiologia , Feminino , Hipocampo/citologia , Hipocampo/fisiopatologia , Humanos , Institucionalização , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/fisiopatologia , Giro Para-Hipocampal/citologia , Giro Para-Hipocampal/patologia , Giro Para-Hipocampal/fisiopatologia , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Células Piramidais/patologia , Esquizofrenia/fisiopatologiaRESUMO
An IgM monoclonal autoantibody (M-protein) with anti-Gal(beta 1-3)GalNAc activity from a patient with lower motor neuron disease bound to the surface of motoneurons isolated from bovine spinal cord. The Gal(beta 1-3)GalNAc epitope is shared by the gangliosides GM1 and GD1b and by several glycoproteins in the nervous system, and binding was abolished by preabsorbing the patient's serum with GM1. Antibodies specific for GM1, however, which do not bind to GaL(beta 1-3)GalNAc, did not bind to the motoneurons. This suggests that Gal(beta 1-3)GalNAc bearing glycoproteins or glycolipids other than GM1 are expressed on the surface of motoneurons, while GM1 may be absent or shielded, and that antibody binding to the cell surface might contribute to the development of the motor neuron disease.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos Glicosídicos Associados a Tumores , Autoanticorpos/imunologia , Dissacarídeos/imunologia , Imunoglobulina M/imunologia , Neurônios Motores/imunologia , Medula Espinal/imunologia , Animais , Bovinos , Membrana Celular/imunologia , Epitopos , Fluorescência , Gangliosídeo G(M1)/imunologia , Gangliosídeos/imunologia , Humanos , Técnicas Imunológicas , Medula Espinal/citologia , Coloração e RotulagemRESUMO
OBJECTIVE: To develop a rapid assay for the detection and measurement of anti-GM(1) ganglioside antibodies in patients with neuropathy, using a surface plasmon resonance-based biosensor. BACKGROUND: Elevated levels of anti-GM(1) ganglioside antibodies are observed in patients with acute and chronic motor neuropathies. Assays for detecting anti-GM(1) antibodies in serum are increasingly being used to help the physician in the evaluation of these patients. METHODS: Antigens were immobilized by adsorption of GM(1) (active) and GM(2) (control) gangliosides onto a dextran-based sensor chip which is in contact with a flow cell carrying the sample. Interaction of specific antibodies directed against GM(1) with the ganglioside-coated sensor chip caused a change in refractive index at the surface of the chip, which was detected by an optical sensor, using the phenomenon of surface plasmon resonance. Sera from patients and healthy individuals were analyzed by the new assay and results were compared with those from ELISA. Anti-GM(1) antibody isotype was identified by using a secondary antibody. RESULTS: The binding of anti-GM(1) antibodies to the immobilized GM(1) was observed in real time after reference subtraction of the response from GM(2) control. The response was proportional to antibody concentration. The assay exhibited high specificity for sera from patients with multifocal motor neuropathy and Guillain-Barré syndrome with antibodies against GM(1). CONCLUSIONS: The surface plasmon resonance biosensor assay offers a rapid system for directly measuring antibody levels in serum without the use of any labels, while comparing favorably with the ELISA system in sensitivity and specificity.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Gangliosídeo G(M1)/sangue , Doenças do Sistema Nervoso/sangue , Ressonância de Plasmônio de Superfície/métodos , Ensaio de Imunoadsorção Enzimática , Humanos , Fatores de TempoRESUMO
A radioimmunoassay (RIA) for measuring isotype-specific antibodies to the myelin-associated glycoprotein (MAG) was developed using radiolabeled CNS MAG in a double-antibody precipitation system. Anti-MAG activity was detected by RIA only in patients with neuropathy and anti-MAG M proteins. Anti-MAG IgM or IgG antibodies were not detected in serum of patients with Guillain-Barré syndrome, chronic relapsing polyneuritis, or multiple sclerosis (MS). Some patients with anti-MAG IgM M proteins also had complexes of IgG or IgA bound to the M protein. In one patient, anti-CNS MAG activity was detected by RIA, but not by ELISA or immunoblot. Anti-MAG antibody activity in patients with neuropathy seems to be isotypically restricted, and there is no evidence for antibody reactivity to MAG in other demyelinating diseases.
Assuntos
Anticorpos Anti-Idiotípicos/análise , Proteínas da Mielina/análise , Radioimunoensaio , Doenças do Sistema Nervoso Central/imunologia , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Técnicas de Imunoadsorção , Proteínas da Mielina/imunologia , Glicoproteína Associada a Mielina , Doenças do Sistema Nervoso Periférico/imunologiaRESUMO
Demyelination of feline sciatic nerve was induced by intraneural injection of serum from three patients with neuropathy and an IgM M-protein that reacted with myelin-associated glycoprotein (MAG). Demyelination exceeded that induced by serum from 18 other individuals, including six IgM M-proteins unreactive with MAG. The myelinolytic effect required active human complement and was abolished by exposure of serum to homogenate of human peripheral nerve that removed 90% of the M-protein. Immunofluorescence studies demonstrated deposition of the injected M-protein and complement on the surface of myelin sheaths, implying that the M-protein reacted with epitopes of myelin exposed to the extracellular space.
Assuntos
Doenças Desmielinizantes/etiologia , Glicoproteínas/imunologia , Imunoglobulina M/imunologia , Proteínas da Mielina/imunologia , Paraproteinemias/imunologia , Animais , Doenças Autoimunes/imunologia , Gatos , Proteínas do Sistema Complemento/análise , Proteínas do Sistema Complemento/imunologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologia , Glicoproteínas/análise , Humanos , Imunoquímica , Imunoglobulina M/análise , Proteínas da Mielina/análise , Glicoproteína Associada a Mielina , Nervos Periféricos/imunologia , Nervos Periféricos/patologiaRESUMO
We report the presence of antisulfatide antibodies in a patient with type I Gaucher's disease and peripheral neuropathy. The association of Gaucher's disease with hypergammaglobulinemia and monoclonal gammopathy is well documented whereas its association with peripheral neuropathy is rare. We discuss whether antibodies directed against the sulfatide antigen are related to Gaucher's disease or are a coincidental association.
Assuntos
Anticorpos/imunologia , Doença de Gaucher/complicações , Doença de Gaucher/imunologia , Doenças do Sistema Nervoso Periférico/complicações , Sulfoglicoesfingolipídeos/imunologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Anti-GM1 antibodies in patients with motor neuropathy or motor neuron disease frequently recognize the Gal(beta 1-3)GalNAc epitope, which is shared by several glycoproteins in peripheral nerve. In this study, cholera toxin (CT), which is specific for GM1, and the lectin peanut agglutinin (PNA), which binds to Gal(beta 1-3)GalNAc-bearing glycoproteins, were used in tissue section and intraneural injection studies to examine the distribution of GM1 and Gal(beta 1-3)GalNAc epitopes in human and rat peripheral nerve by epifluorescence and confocal microscopy. In tissue sections, CT stained the compact myelin in both human and rat nerves, whereas PNA was localized at the outer edge of the myelin sheath or Schwann cell membrane. Following intraneural injection into rat sciatic nerves, both CT and PNA bound to the nodes of Ranvier, although CT was concentrated in the paranodal myelin region whereas PNA was concentrated at the nodal gap. These structures may be targets for anti-GM1 antibodies in peripheral nerve.
Assuntos
Antígenos Glicosídicos Associados a Tumores/imunologia , Epitopos/análise , Gangliosídeo G(M1)/imunologia , Nervos Periféricos/química , Animais , Arachis , Toxina da Cólera/farmacocinética , Humanos , Lectinas/farmacocinética , Microscopia de Fluorescência , Aglutinina de Amendoim , Lectinas de Plantas , Ratos , Valores de Referência , Nervo Isquiático/química , Coloração e Rotulagem , Nervo Sural/químicaRESUMO
IgM M-proteins have been found in patients with axonal neuropathies, but it is not known whether these M-proteins bind to nerve components or actually cause the neuropathy. In one patient with axonal neuropathy studied, the IgM M-protein bound to chondroitin sulfate, and there were deposits of IgM in the endoneurium of the patient's nerve. A monoclonal anti-idiotype antibody generated against that M-protein was used to study the binding of the M-protein to normal nerve and to distinguish it from binding of other IgM species that might be present in the patient's serum. In immunofluorescence studies, the M-protein bound to the endoneurium in normal nerve and to connective tissue in other organs. In immunoblot studies, the M-protein bound to several protein bands in nerve and other tissues. The data suggest that the M-protein bound to mucopolysaccharides in nerve endoneurium and connective tissue.
Assuntos
Axônios , Glicoproteínas/análise , Imunoglobulina M/análise , Doenças do Sistema Nervoso/imunologia , Anticorpos Monoclonais , Axônios/análise , Humanos , Idiótipos de Imunoglobulinas , Imunoglobulina M/imunologiaRESUMO
Immunohistochemical binding of IgM paraproteins to nerve was studied using the immunoperoxidase technique with serum from 10 patients with benign plasma cell dyscrasia and neuropathy. We stained the myelin sheaths of peripheral nerves and roots fo five patients who had myelin-absorbable IgM paraproteins. Two patients with IgM paraproteins that did not react with myelin showed predominant staining of axons, while three were completely negative. Serum specimens from normal volunteers and patients with paraproteinemias or ALS were also unreactive. Immunocytochemical methods can detect IgM paraproteins with an affinity for nerve antigens and may assist in the diagnosis and classification of plasma cell dyscrasia associated neuropathy.
Assuntos
Paraproteinemias/imunologia , Nervos Periféricos/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Plexo Braquial/imunologia , Humanos , Técnicas Imunoenzimáticas , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Proteínas da Mielina/imunologia , Paraproteinemias/patologia , Paraproteínas/imunologia , Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/patologia , Medula Espinal/imunologia , Raízes Nervosas Espinhais/imunologiaRESUMO
Two patients with neuropathy and IgM paraproteinemia displayed different immunoreactivity to acidic peripheral nerve glycolipids. In one patient, immunostaining on thin-layer chromatographic plate revealed binding of the IgM to sulfated glucuronosyl paragloboside (SGPG) and sulfated glucuronosyl lactosaminyl paragloboside (SGLPG). The other IgM bound SGPG, SGLPG, and a new third glycolipid. Immunoreactivity of the IgM varies in this syndrome.
Assuntos
Glicolipídeos/imunologia , Imunoglobulina M/imunologia , Paraproteinemias/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Idoso , Cromatografia em Camada Fina , Glicolipídeos/isolamento & purificação , Humanos , Imunoglobulina M/isolamento & purificação , Masculino , Músculos/fisiopatologia , Paraproteinemias/complicações , Paraproteinemias/fisiopatologia , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ligação ProteicaRESUMO
We induced progressive conduction block in feline sciatic nerve by endoneurial injection of serum from 2 patients with demyelinating neuropathy and an anti-myelin-associated glycoprotein (MAG) IgM M protein. The block was longlasting (up to 4 days) and affected about half the motor nerve fibers. Control serum from patients with an IgM M protein that did not react with MAG produced a transient block (less than 48 hours) that affected an average of 25% of motor fibers. Nerves with sustained block showed widespread demyelination of many nerve fibers, exceeding controls. The findings support the view that chronic demyelinating neuropathy in these patients is caused by the anti-MAG M protein.
Assuntos
Proteínas Sanguíneas/análise , Doenças Desmielinizantes/sangue , Imunoglobulina M , Imunoglobulinas , Bainha de Mielina/fisiologia , Animais , Proteínas Sanguíneas/imunologia , Gatos , Eletrofisiologia , Imunofluorescência , Humanos , Lisofosfatidilcolinas/farmacologia , Proteínas da Mielina/imunologia , Bainha de Mielina/ultraestrutura , Glicoproteína Associada a Mielina , Bloqueio Nervoso , Condução Nervosa/efeitos dos fármacos , Valores de Referência , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiologia , Fatores de TempoRESUMO
We reviewed the clinical and electrophysiologic features of 36 patients with increased titers of IgM anti-GM1 antibodies. Mildly elevated titers of up to 3,200 were not associated with any particular clinical syndrome or disease. Clinically, 14 of 16 patients with highly elevated titers of 6,400 or higher had progressive weakness with lower motor neuron signs; six had active tendon reflexes and eight had absent reflexes, but none had definite upper motor neuron signs. Electrophysiologic studies showed spontaneous activity in all 14 patients, one or more motor conduction blocks in nine, slowed motor conductions in one, and normal conductions in four patients. None had abnormal sensory conductions. These patients presented with a syndrome that has features of, but is distinct from, both motor neuron disease and demyelinating neuropathy.
Assuntos
Anticorpos/análise , Gangliosídeo G(M1)/imunologia , Doenças do Sistema Nervoso/imunologia , Adulto , Idoso , Eletrofisiologia , Feminino , Humanos , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , Atividade Motora , Doença dos Neurônios Motores/imunologia , Doenças do Sistema Nervoso/fisiopatologia , Condução Nervosa , Paraproteinemias/imunologia , Reflexo de Estiramento/fisiologiaRESUMO
In some patients with neuropathy and plasma cell dyscrasia, the M-proteins bind to peripheral nerves. Binding of M-proteins to peripheral nerve glycolipids was examined by immunostaining after thin-layer chromatography. The IgM from 16 patients with anti-MAG M-proteins bound to the same two glycolipid bands in peripheral nerve. The IgM that bound to the glycolipids had the same idiotype as the anti-MAG M-protein, indicating that it was the M-protein that bound to both glycolipids. The reactive glycolipids did not contain sialic acid and were not gangliosides. No immunostaining of peripheral nerve glycolipids was observed with IgM from patients with neuropathy and IgM M-proteins that did not bind to MAG, and the anti-MAG antibodies did not bind to brain glycolipids. Anti-MAG M-proteins probably bind to the same or closely related carbohydrate determinants that are shared by a number of glycoproteins and glycolipids of peripheral nerve.
Assuntos
Imunoglobulina M/metabolismo , Proteínas da Mielina/metabolismo , Paraproteinemias/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Anticorpos/metabolismo , Glicolipídeos/metabolismo , Humanos , Proteínas da Mielina/imunologia , Glicoproteína Associada a Mielina , Paraproteinemias/imunologia , Doenças do Sistema Nervoso Periférico/imunologiaRESUMO
In some patients with plasma cell dyscrasia and neuropathy, there are IgM M proteins that react with the myelin-associated glycoprotein (MAG). We used an enzyme-linked immunosorbent assay (ELISA) system to detect anti-MAG IgM antibodies. Reactivity with human MAG by ELISA correlated with demonstration of anti-MAG IgM antibodies by the "immunoblot" technique. Human MAG was more effective than bovine MAG as antigen, and there was no significant reactivity with mouse MAG. The ELISA system is a simple and convenient method for detecting anti-MAG IgM antibodies.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Doenças Desmielinizantes/imunologia , Imunoglobulina M/imunologia , Proteínas da Mielina/imunologia , Doenças Desmielinizantes/complicações , Ensaio de Imunoadsorção Enzimática , Humanos , Glicoproteína Associada a Mielina , Paraproteinemias/complicações , Paraproteinemias/imunologiaRESUMO
OBJECTIVE: To investigate the clinical and electrophysiologic characteristics of the neuropathy associated with elevated serum antisulfatide antibodies. METHODS: Clinical, electrophysiologic, morphologic, and laboratory data of 25 patients with significantly elevated (>25,600) antisulfatide antibodies were reviewed. RESULTS: Four groups were distinguished based on clinical and electrophysiologic data: Group 1, eight patients with predominantly small fiber sensory neuropathy (32%); Group 2, five patients with mixed large and small fiber sensory neuropathy (20%); Group 3, seven patients with axonal sensorimotor neuropathy (28%); and Group 4, three patients with demyelinating sensorimotor neuropathy (12%). One additional patient had mononeuritis multiplex and one had ALS. An immunoglobulin M (IgM) monoclonal gammopathy was found in 30% of the patients tested, but not in any of the Group 1 patients with small fiber sensory neuropathy. Serum IgM level was elevated in 12 patients, of whom six had a concomitant monoclonal gammopathy. Morphologic studies in five patients showed predominantly axonal degeneration, with three of the patients also exhibiting additional features of demyelination. CONCLUSIONS: Antisulfatide antibodies are associated with several subtypes of peripheral neuropathy. Predominantly sensory or sensorimotor axonal neuropathies are most common in this series, with the sensory component either small fiber or mixed fiber type. A smaller demyelinating group indistinguishable from patients with chronic inflammatory demyelinating polyradiculopathy was also seen. One third of patients had a concomitant IgM monoclonal gammopathy, and approximately one half had elevated serum IgM.