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1.
J Immunol Res ; 2015: 450391, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26065001

RESUMO

Polyneuropathy associated with IgM monoclonal gammopathy and anti-myelin associated glycoprotein (MAG) antibodies is an immune-mediated demyelinating neuropathy. The pathophysiology of this condition is likely to involve anti-MAG antibody deposition on myelin sheaths of the peripheral nerves and it is supposed to be distinct from chronic inflammatory demyelinating neuropathy (CIDP), another immune-mediated demyelinating peripheral neuropathy. In this series, we have retrospectively reviewed clinical and laboratory findings from 60 patients with polyneuropathy, IgM gammopathy, and anti-MAG antibodies. We found that the clinical picture in these patients is highly variable suggesting a direct link between the monoclonal gammopathy and the neuropathy. Conversely, one-third of patients had a CIDP-like phenotype on electrodiagnostic testing and this was correlated with a low titer of anti-MAG antibodies and the absence of widening of myelin lamellae. Our data suggest that polyneuropathy associated with anti-MAG antibodies is less homogeneous than previously said and that the pathophysiology of the condition is likely to be heterogeneous as well with the self-antigen being MAG in most of the patients but possibly being another component of myelin in the others.


Assuntos
Anticorpos Monoclonais/imunologia , Autoanticorpos/imunologia , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/imunologia , Nervos Periféricos/imunologia , Estudos Retrospectivos
2.
Clin Lab ; 59(11-12): 1277-87, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24409662

RESUMO

BACKGROUND: To assess the performance of commercial anti-ganglioside antibody assays, we determined anti-ganglioside antibody IgG and IgM isotype profiles of patients with acute and chronic well-characterized immune-mediated peripheral neuropathies by one immunodot assays (Zentec/Ingen: Dotzen Ganglio Profile Ab, Euroimmun/BioAdvance: Euroline ganglioprofile), two line-immuno assay (GA Generic Assays/Labodia: Anti-Gangli osid Dot, Euroimmun/BioAdvance: Euroline ganglioprofile), and one enzyme-linked immunosorbent assay (ELISA) (Bühlmann: GanglioCombi). Specific antibody profiles were compared with those obtained by our validated standard in-house immunodot assay (IDA). METHODS: We selected 33 sera with high levels of IgG and IgM anti-ganglioside antibodies from 15 patients with Guillain-Barre syndrome (GBS) subtypes and variants, 12 patients with CANOMAD syndrome (chronic ataxic neuropathy with ophthalmoplegia, M-paraprotein, cold agglutinins, disialosyl antibodies), 5 patients with chronic motor peripheral neuropathies, and 1 patient with sensory neuropathy and a control group composed of 10 patients with non-autoimmune neuropathy. RESULTS: The 3 commercial IDAs employing hydrophobic membranes and the ELISA demonstrated different carbohydrate epitopes on 6 to 12 glycolipid antigens used for anti-ganglioside antibody detection. Comparison with the validated in-house IDA showed large variations in sensitivity between tests and a more diverse reactivity to gangliosides than expected. The test with the largest panel of glycolipids detecting 11 anti-ganglioside antibody reactivities (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, and sulfatide) revealed the best concordance with our in-house assay. However, even with this test, differences were observed in the immunoreactivity against some gangliosides and weakly stained bands were not easy to interpret. CONCLUSIONS: Our data suggest an urgent need for standardization of commercial anti-ganglioside assays and the introduction of international anti-ganglioside antibody reference standards.


Assuntos
Autoanticorpos/sangue , Gangliosídeos/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Kit de Reagentes para Diagnóstico , Ensaio de Imunoadsorção Enzimática , Humanos , Doenças do Sistema Nervoso Periférico/sangue
3.
Ann Biol Clin (Paris) ; 69(4): 476-80, 2011.
Artigo em Francês | MEDLINE | ID: mdl-21896416

RESUMO

We reported the laboratory phenotype of a monoclonal IgM-lambda against disialylated gangliosides, in a 81-year-old man admitted to a neurological department because of the progressive development of distal paresthesias, gait unsteadiness, difficulty to walk and having falls. Serological studies revealed an IgM monoclonal protein with lambda light chain component of MGUS type. IgM level was 4 g/L. The positive laboratory studies showed high titers of IgM antibodies in excess of 1/10(5) against specific disialylated gangliosides including GD1b, GD3, GT1b and GQ1b. There was no serum IgM binding to MAG and SGPG/SGLPG. Clonality by in-house immunodot of ganglioside antibodies was demonstrated using kappa and lambda light chain specific antibodies. Light chain subtype of the anti-ganglioside antibody activity and monoclonal IgM was lambda subtype. The reactivity at high titers was against gangliosides containing the disialosyl epitope. The clinical and laboratory features have been described under the acronym CANOMAD: Chronic Ataxic Neuropathy with Ophthalmoplegia, M proteins, cold Agglutinins and Disialosyl antibodies. Administration of IVIg produced a significant neurological improvement during six years. Then the neuropathy became refractory in the IVIg and worsened in severity, a cure by Rituximab® was established. The patient died from a pneumopathy only two months later. Monoclonal IgM binding to disialylated gangliosides have high level of specificity for diagnosis of the CANOMAD syndrome.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/imunologia , Anticorpos Monoclonais/sangue , Ataxia/diagnóstico , Ataxia/imunologia , Gangliosídeos/sangue , Imunoglobulina M/sangue , Oftalmoplegia/diagnóstico , Oftalmoplegia/imunologia , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Ataxia/sangue , Ataxia/complicações , Ataxia/tratamento farmacológico , Evolução Fatal , Marcha Atáxica/etiologia , Gangliosídeos/metabolismo , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Ácido N-Acetilneuramínico/metabolismo , Oftalmoplegia/sangue , Oftalmoplegia/complicações , Oftalmoplegia/tratamento farmacológico , Parestesia/etiologia , Nervos Periféricos/metabolismo , Rituximab , Falha de Tratamento
4.
J Neurol ; 258(11): 1958-64, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21516465

RESUMO

We describe by an in-house dot immunoassay, specific anti-ganglioside and sulfatide antibodies, by comparing the results from a large group of 134 infected French GBS patients and those from 172 noninfected French GBS and 142 control groups. A recent infection was identified in 134/306 (43.8%) GBS patients: Campylobacter jejuni (24.6%) was the most common agent, followed by cytomegalovirus (12.4%), Mycoplasma pneumoniae (3.2%) and Epstein-Barr virus (1.3%). Anti-ganglioside antibodies were detected in 97/306 (31.7%) of total GBS patients, 82/134 (61.2%) of GBS patients with a recent identified infection and 15/172 (8.7%) of the patients without identified infection. According to the specificities and antibody classes, four specific IgG antibody profiles were individualised against the two major GM1 and GD1a gangliosides in motor axonal C. jejuni-associated GBS variants, against GQ1b and disialylated gangliosides in Miller Fisher syndrome and its variants. One specific IgM profile against GM2 was found in 16/38 (42%) of severe sensory demyelinating CMV-associated GBS and in 8/17 (47%) of subjects with recent CMV infection with no neurological disease. IgG or IgM antibodies to GM1 were found in 5/10 M. pneumoniae-infected patients. IgM antibodies to GM1 were observed in the control groups, 15% of the 74 patients with amyotrophic lateral sclerosis, 19% of the 51 patients with chronic inflammatory demyelinating polyneuropathy, and 9% of the 21 healthy control subjects. The fine specificity of the four IgG antibody profiles and the IgM anti-GM2 profile is closely related to the nature of the preceding infections and the pattern of clinical features.


Assuntos
Autoanticorpos/sangue , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/microbiologia , Infecções/complicações , Anticorpos Antibacterianos/análise , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Infecções por Campylobacter/imunologia , Infecções por Citomegalovirus/imunologia , Feminino , Síndrome de Guillain-Barré/sangue , Humanos , Immunoblotting , Imunoglobulina G/análise , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/análise , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Infecções/imunologia , Masculino , Pessoa de Meia-Idade , Pneumonia por Mycoplasma/imunologia
5.
Clin Infect Dis ; 52(7): 837-44, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21427390

RESUMO

BACKGROUND: Little is known about the epidemiology and the prognostic factors of Guillain-Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). METHODS: We prospectively followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. RESULTS: Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P=.052). The main factors associated with long-term neurological sequelae (21%) were older age (P<.001) and assisted ventilation during hospitalization (P=.005). The number of CMV-GBS cases decreased between 1996 and 2006 (P=.019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). CONCLUSIONS: This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.


Assuntos
Infecções por Citomegalovirus/complicações , Síndrome de Guillain-Barré/epidemiologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Estudos de Coortes , DNA Viral/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
6.
Ann Biol Clin (Paris) ; 68(6): 675-80, 2010.
Artigo em Francês | MEDLINE | ID: mdl-21159581

RESUMO

We evaluated the analytical performances of a new line immunoassay (LIA) for the simultaneous detection of twelve anti-ganglioside and anti-sulfatide autoantibodies from Generic Assays, in comparison with our dot immunoassay. The LIA detected IgG and/or IgM autoantibodies against human GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b and sulfatide. Forty sera of patients with IgG autoantibody profiles in acute autoimmune neuropathies and 39 sera of patients with IgM autoantibody profiles in chronic autoimmune neuropathies were tested. To have a better sensitivity, 20 µL of sera instead of 10 µL were used. In these conditions, we observed a good concordance of IgG and IgM autoantibody profiles by both immunoassays. The test including novel gangliosides was easy to perform and superior for identifying autoimmune neuropathies. The data indicate that the test provides reliable simultaneous detection of autoantibodies against a large panel of human gangliosides and sulfatide with a good diagnostic usefulness in combination with clinical and electrophysiological data.


Assuntos
Autoanticorpos/sangue , Gangliosídeos/imunologia , Imunoensaio/métodos , Doenças do Sistema Nervoso Periférico/imunologia , Sulfoglicoesfingolipídeos/imunologia , Humanos , Doenças do Sistema Nervoso Periférico/sangue
7.
Ann Biol Clin (Paris) ; 68(3): 351-4, 2010.
Artigo em Francês | MEDLINE | ID: mdl-20478781

RESUMO

We report a case of a 68-year-old man with classical triad, ophthalmoplegia, ataxia and areflexia in uncommon context. Our patient presented initial symptoms during radiation therapy for prostate cancer. After elimination of brainstem stroke and carcinomatous meningitidis by his general physician, he was referred with a provisional diagnosis of Miller-Fisher syndrome (MFS). The main characteristics of this case of MFS were uncommon: antecedent illness of urinary tract infections by Pseudomonas aeruginosa, presence of high titres of IgG antibodies directed against Mycoplasma pneumoniae, CSF pleocytosis and intrathecal IgG synthesis, serum and CSF monoclonal IgG in a monoclonal gammopathy of undetermined significance (MGUS). The serum and CSF immunological marker of MFS was a monoclonal IgG antibody targeting the ganglioside GQ1b with abundant expression on oculomotor nerves.


Assuntos
Anticorpos Monoclonais/sangue , Gangliosídeos/imunologia , Cadeias lambda de Imunoglobulina/sangue , Síndrome de Miller Fisher/diagnóstico , Idoso , Humanos , Masculino
9.
Clin Infect Dis ; 48(1): 48-56, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19025491

RESUMO

BACKGROUND: In Western countries, the cause of 60% of all Guillain-Barré syndrome (GBS) cases remains unidentified. The number of cases of unidentified cause peaks in winter, and these cases are commonly preceded by respiratory tract infection or influenza-like illness. We investigated the triggering role of influenza virus infection. METHODS: Of 405 patients with GBS who were admitted to a French reference center during 1996-2004, 234 had cases caused by an unidentified agent. We used time-series methods to study the correlation between the monthly incidence of such cases and influenza-like illnesses reported by the Sentinelles surveillance network. We analyzed anti-influenza antibodies using complement fixation testing and hemagglutination-inhibition assays. We studied etiological subgroups using Wilcoxon and Fisher's exact tests. RESULTS: We found a positive association between the monthly incidence of GBS caused by an unidentified agent and reported influenza-like illnesses. Of 73 patients whose cases occurred during periods in which there was a possible link to influenza, 10 (13.7%) had serological evidence of recent influenza A, and 4 (5.5%) had serological evidence of influenza B. Eight of 10 influenza A-related cases occurred during "major" influenza seasons, and antibodies specific to the current epidemic strain were found in 9 cases. Most patients with influenza A-related cases were aged < 65 years, and none had antiganglioside antibodies. Influenza-related cases differed both from Campylobacter jejuni-related cases, with regard to the lack of need for mechanical ventilation (P = .014), and from the cases caused by an unidentified agent, with regard to the presence of preceding influenza-like illness or respiratory tract infection (P = .015) and longer time from the infectious event to GBS onset (P = .04). CONCLUSIONS: Influenza viruses are infrequent triggering agents of GBS but may play a significant role during major influenza outbreaks. Influenza-related GBS displays specific features and is not associated with antiganglioside antibody response, which suggests the presence of underlying immune mechanisms.


Assuntos
Síndrome de Guillain-Barré/etiologia , Influenza Humana/complicações , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Testes de Fixação de Complemento , Feminino , França , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/epidemiologia , Testes de Inibição da Hemaglutinação , Humanos , Incidência , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estações do Ano , Estatística como Assunto
11.
Pathol Biol (Paris) ; 53(2): 68-74, 2005 Mar.
Artigo em Francês | MEDLINE | ID: mdl-15708649

RESUMO

The purpose of this paper is to report cerebrospinal fluid (CSF) findings in multiple sclerosis (MS) from our laboratory, to discuss the implications of CSF abnormalities in terms of diagnosis. Paired CSF-serum samples from of 1533 on 3893 patients with suspected neurological diseases over a 10 year period were analysed by routine laboratory microscopy and assays of immunoglobulin G by isoelectric focusing for the detection of intrathecal oligoclonal IgG. Patients were grouped further into four headings according to their disorders: MS (625 cases), definite (246 cases) probable (123 cases) and possible (256 cases) according to Poser, others inflammatory neurological diseases (91 cases), various non-inflammatory neurological disorders (732 cases) and uncertain neurological disorders (85 cases). Definite MS group (16%) was compared to non-inflammatory neurological disorders (48%). Important signs for activity of multiple sclerosis are observed. Cell counts were 10/microl in 71% (N < or =2/microl). Inflammatory cytology is observed after concentration and cytocentrifugation on slides with activated B-lymphocytes, lymphoplasmocytes and/or plasmocytes (76%), total protein concentration is increased in 37% (N < 0.40g/l), CSF/serum albumin quotient with age dependent references for the blood-CSF barrier dysfunction is increased in 26% (N < 0.65 x 10(-2)), IgG index for intrathecal synthesis of IgG is increased in 69% (N < 0.70), sensitive detection of oligoclonal IgG restricted to CSF by isoelectric focusing is positive in 91% (86-96%) with a specificity of 96% (93-99%).


Assuntos
Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Diagnóstico Diferencial , Humanos , Imunoglobulina G/sangue , Inflamação/líquido cefalorraquidiano , Esclerose Múltipla/sangue , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
J Infect Dis ; 157(6): 1226-34, June 1988.
Artigo em Inglês | MedCarib | ID: med-10056

RESUMO

Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strenghten the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies. (AU)


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Anticorpos Antivirais/biossíntese , Infecções por Deltaretrovirus/imunologia , Deltaretrovirus/imunologia , Imunoglobulina G/biossíntese , Paralisia/imunologia , Doenças da Medula Espinal/imunologia , Estudo Comparativo , Anticorpos Antivirais , Barreira Hematoencefálica , Guiana Francesa , Infecções por Deltaretrovirus , Imunoglobulina G , Imunoensaio , Côte d'Ivoire , Espasticidade Muscular , Paralisia , Senegal , Doenças da Medula Espinal , Clima Tropical , Índias Ocidentais
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