RESUMEN
Background/Objective: Myasthenia Gravis (MG) is an autoimmune disorder characterized by pathogenic autoantibodies (AAbs) targeting nicotinic acetylcholine receptors (AChR), disrupting neuromuscular communication. RadioImmunoPrecipitation Assay (RIPA) is recommended to detect AChR AAbs, but its complexity and radioactive requirements limit widespread use. We compare non-RIPA anti-AChR immunoassays, including Cell-Based Assay (CBA) and two ELISA kits, against the gold standard RIPA. Methods/Results: 145 samples were included with medical indication for anti-AChR testing. By the RIPA method, 63 were negative (RIPA-Neg <â0.02 nmol/L), 18 were classified as Borderline (≥0.02 -1 nmol/L), and 64 were positive (RIPA-Posâ>â1 nmol/L). The competitive ELISA showed poor agreement with RIPA (Kappaâ=â0.216). The indirect ELISA demonstrated substantial agreement with RIPA (Kappaâ=â0.652), with â¼76% sensitivity and â¼94% specificity for MG diagnostic. The CBA, where fixed cells expressing clustered AChR were used as substrate, exhibited almost perfect agreement with RIPA (Kappaâ=â0.984), yielding â¼98% sensitivity and 96% specificity for MG. In addition, a semiquantitative analysis showed a strong correlation between CBA titration, indirect ELISA, and RIPA levels (râ=â0.793 and râ=â0.789, respectively). Conclusions: The CBA displayed excellent analytical performance for MG diagnostic when compared to RIPA, making it a potential replacement for RIPA in clinical laboratories. Some solid-phase assays (such as the indirect ELISA applied here), as well as CBA titration, offer reliable options to estimate anti-AChR AAb levels after confirming positivity by the CBA.â¥.
Asunto(s)
Autoanticuerpos , Ensayo de Inmunoadsorción Enzimática , Miastenia Gravis , Ensayo de Radioinmunoprecipitación , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Miastenia Gravis/inmunología , Miastenia Gravis/diagnóstico , Sensibilidad y Especificidad , Receptores Colinérgicos/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Adulto JovenRESUMEN
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.
INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Citocinas/sangre , Interleucina-6 , Miastenia Gravis/diagnóstico , Miastenia Gravis/inmunología , Miastenia Gravis/tratamiento farmacológico , Prednisona/uso terapéutico , Recolección de Muestras de Sangre , Debilidad MuscularRESUMEN
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. The aim of this study was to evaluate clinical, epidemiological and serological features of patients with MG in a Public Hospital of Buenos Aires City. A retrospective analysis of 190 patients diagnosed with MG was performed. The mean age of MG onset was 38 years, 30% had late-onset MG (onset age > 50 years). The female/male ratio was 1.7 / 1. Disease started earlier in women than in men, mean 32 vs. 48 years (p < 0.0001). Familial autoimmune MG represented 3.2% of the cases. Most of the patients initiated their disease with a pure ocular form (52%). 12.1% (23/190) were considered ocular MG at follow-up. Thymoma-associated MG represented 11.6% of cases. 27.1% had other associated autoimmune disease, thyroid disorders were the most frequent. 81.4% were anti-acetylcholine receptor antibody (AChR-ab) positive MG; 22.7% of AChR-ab negatives were positive for anti-muscle specific kinase (MusK) antibodies. Clinical outcome was relatively good; more than half of cases were in remission or minimal manifestations at the last visit. The majority of patients required immunosuppression to control the symptoms, 78% received corticosteroids and 48%, a non-steroidal immunosuppressant.
La miastenia gravis (MG) es una enfermedad autoinmune mediada por anticuerpos dirigidos contra proteínas post sinápticas de la unión neuromuscular. El objetivo de este estudio fue describir los aspectos clínicos, epidemiológicos y serológicos de pacientes con MG en un Hospital Público de la Ciudad de Buenos Aires. Se realizó un análisis retrospectivo sobre 190 enfermos con diagnóstico de MG. La edad media de inicio de la enfermedad fue de 38 años; 57 (30%) fueron MG de inicio tardío (inicio de síntomas > 50 años). La relación mujer/hombre fue 1.7/1. La enfermedad se inició más tempranamente en las mujeres que en los hombres, media 32 vs. 48 años (p < 0.0001). La MG familiar autoinmune representó el 3.2 % (6 casos). La forma más común de presentación fue con manifestaciones oculares puras (52%). El 12.1% (23/190) fue considerada MG ocular en el seguimiento. La MG asociada a timoma se presentó en 22 casos (11.6%). El 27.1% presentó otra enfermedad autoinmune asociada, siendo las tiroideas las más frecuentes. El 81.4% tuvo anticuerpos antireceptores de acetilcolina (ACRA) positivos y 22.7% de los ACRA negativos fueron positivos para anticuerpos anti-tirosina quinasa musculo especifica (anti-MusK). La evolución clínica fue favorable, hallándose más de la mitad de los casos en remisión o manifestaciones mínimas en la última visita. La mayoría requirió inmunosupresión para control de la sintomatología, el 78% recibió corticoides y el 48% un inmunosupresor no esteroideo.
Asunto(s)
Miastenia Gravis/epidemiología , Adolescente , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Enfermedades Autoinmunes/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/inmunología , Prevalencia , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Estudios Retrospectivos , Distribución por Sexo , Factores Sexuales , Adulto JovenRESUMEN
La miastenia gravis (MG) es una enfermedad autoinmune mediada por anticuerpos dirigidos contra proteínas post sinápticas de la unión neuromuscular. El objetivo de este estudio fue describir los aspectos clínicos, epidemiológicos y serológicos de pacientes con MG en un Hospital Público de la Ciudad de Buenos Aires. Se realizó un análisis retrospectivo sobre 190 enfermos con diagnóstico de MG. La edad media de inicio de la enfermedad fue de 38 años; 57 (30%) fueron MG de inicio tardío (inicio de síntomas > 50 años). La relación mujer/hombre fue 1.7/1. La enfermedad se inició más tempranamente en las mujeres que en los hombres, media 32 vs. 48 años (p < 0.0001). La MG familiar autoinmune representó el 3.2 % (6 casos). La forma más común de presentación fue con manifestaciones oculares puras (52%). El 12.1% (23/190) fue considerada MG ocular en el seguimiento. La MG asociada a timoma se presentó en 22 casos (11.6%). El 27.1% presentó otra enfermedad autoinmune asociada, siendo las tiroideas las más frecuentes. El 81.4% tuvo anticuerpos anti-receptores de acetilcolina (ACRA) positivos y 22.7% de los ACRA negativos fueron positivos para anticuerpos anti-tirosina quinasa musculo especifica (anti-MusK). La evolución clínica fue favorable, hallándose más de la mitad de los casos en remisión o manifestaciones mínimas en la última visita. La mayoría requirió inmunosupresión para control de la sintomatología, el 78% recibió corticoides y el 48% un inmunosupresor no esteroideo.
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. The aim of this study was to evaluate clinical, epidemiological and serological features of patients with MG in a Public Hospital of Buenos Aires City. A retrospective analysis of 190 patients diagnosed with MG was performed. The mean age of MG onset was 38 years, 30% had late-onset MG (onset age > 50 years). The female/male ratio was 1.7 / 1. Disease started earlier in women than in men, mean 32 vs. 48 years (p < 0.0001). Familial autoimmune MG represented 3.2% of the cases. Most of the patients initiated their disease with a pure ocular form (52%). 12.1% (23/190) were considered ocular MG at follow-up. Thymoma-associated MG represented 11.6% of cases. 27.1% had other associated autoimmune disease, thyroid disorders were the most frequent. 81.4% were anti-acetylcholine receptor antibody (AChR-ab) positive MG; 22.7% of AChR-ab negatives were positive for anti-muscle specific kinase (MusK) antibodies. Clinical outcome was relatively good; more than half of cases were in remission or minimal manifestations at the last visit. The majority of patients required immunosuppression to control the symptoms, 78% received corticosteroids and 48%, a non-steroidal immunosuppressant.
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Miastenia Gravis/epidemiología , Argentina/epidemiología , Enfermedades Autoinmunes/epidemiología , Factores Sexuales , Prevalencia , Estudios Retrospectivos , Receptores Colinérgicos/inmunología , Distribución por Sexo , Proteínas Tirosina Quinasas Receptoras/inmunología , Edad de Inicio , Distribución por Edad , Miastenia Gravis/inmunologíaRESUMEN
The relevance of polyautoimmunity, defined as the presence of 2or more autoimmune diseases in the same individual, is one of the issues not yet elucidated in medical practice. The coexistence of myasthenia gravis (MG) and systemic lupus erythematosus (SLE) is a clinical challenge due to the possible differential diagnoses of muscle involvement in patients with SLE. We present the case of a patient who came to the emergency room of Hospital Universitario San Ignacio in Bogotá, Colombia, with a previous diagnosis of SLE, who developed acute weakness in the context of a systemic infection, with a clinical and electrophysiological diagnosis of MG.
Asunto(s)
Autoinmunidad , Lupus Eritematoso Sistémico/complicaciones , Miastenia Gravis/complicaciones , Femenino , Humanos , Lupus Eritematoso Sistémico/inmunología , Miastenia Gravis/inmunología , Adulto JovenRESUMEN
Myasthenia gravis is an acquired autoimmune disorder of the neuromuscular junction characterized by fluctuating weakness and fatigability of skeletal muscles. The diagnosis can be established by clinical and serologic testing, with predominance of autoantibodies against the acetylcholine receptor, and Muscle-specific kinase antibodies. We report two cases of Myasthenia gravis, the first one is a 31 year old patient with a debut of the disease, mainly with bulbar symptoms, and the second one is a 29 year old patient diagnosed with generalized Miasthenia Gravis also mainly with bulbar symptoms with worsening of symptomatology. In this report treatments alternatives and management approaches are discused
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Humanos , Femenino , Adulto , Miastenia Gravis/inmunología , Miastenia Gravis/tratamiento farmacológico , Bromuro de Piridostigmina/uso terapéutico , Timectomía , Inmunoglobulinas Intravenosas/uso terapéutico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Inmunoterapia , Miastenia Gravis/cirugía , Miastenia Gravis/clasificaciónRESUMEN
The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system, nAChRs contribute to the pathological mechanisms of neurodegenerative disorders, such as Alzheimer and Parkinson diseases. In the peripheral nerve-muscle synapse, the vertebrate neuromuscular junction, "classical" myasthenia gravis (MG) and other forms of neuromuscular transmission disorders are antibody-mediated autoimmune diseases. In MG, antibodies to the nAChR bind to the postsynaptic receptors and activate the classical complement pathway culminating in the formation of the membrane attack complex, with the subsequent destruction of the postsynaptic apparatus. Divalent nAChR-antibodies also cause internalization and loss of the nAChRs. Loss of receptors by either mechanism results in the muscle weakness and fatigability that typify the clinical manifestations of the disease. Other targets for antibodies, in a minority of patients, include muscle specific kinase (MuSK) and low-density lipoprotein related protein 4 (LRP4). This brief Review analyzes the current status of muscle-type nAChR in relation to the pathogenesis of autoimmune diseases affecting the peripheral cholinergic synapse.
Asunto(s)
Autoanticuerpos/inmunología , Miastenia Gravis/inmunología , Unión Neuromuscular/inmunología , Receptores Nicotínicos/inmunología , Animales , Humanos , Transmisión Sináptica/inmunologíaRESUMEN
BACKGROUND: We investigated the prognosis of patients with myasthenia gravis (MG) initially presenting with only ocular symptoms in an Argentinian population. SUMMARY: We performed a retrospective analysis of 61 patients with MG with pure ocular involvement at onset. Generalized MG (gMG) developed in 73.7% of patients, while the rest only exhibited ocular symptoms throughout the course of the disease (ocular MG [oMG]). The AChR antibody (AChR-ab) was found in 81.4% of the gMG and 50% of the oMG cases. AChR-ab titers were also significantly higher in the gMG than in the oMG group. Patients with oMG more frequently required treatment only with acetylcholinesterase inhibitors and showed more remissions. Key Messages: Our study showed high generalization in patients with MG debuting with ocular symptoms. Patients with AChR seropositivity and higher AChR-ab titers had an increased risk for gMG, while patients with oMG showed lower corticosteroid requirements and a higher remission rate.
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Miastenia Gravis/complicaciones , Adulto , Argentina/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/epidemiología , Miastenia Gravis/inmunología , Pronóstico , Estudios RetrospectivosRESUMEN
Primary Biliary Cirrhosis and Myasthenia Gravis are both autoimmune conditions, however, there are only rare case reports of their association. This is a case report of acetylcholine receptor antibody positive generalized myasthenia gravis in a female patient with antimitochondrial antibody positive, liver biopsy-confirmed primary biliary cirrhosis.
Asunto(s)
Anticuerpos/sangre , Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/inmunología , Miastenia Gravis/epidemiología , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , Biopsia , Comorbilidad , Femenino , Humanos , Hígado/patología , Cirrosis Hepática Biliar/patología , Persona de Mediana Edad , Mitocondrias Hepáticas/inmunología , Miastenia Gravis/sangreRESUMEN
Myasthenia gravis is an autoimmune disease characterized by weakness and fatigue of the skeletal muscles of the face and extremities. Pregnancy is associated with 19-41% of exacerbations. We present a 19-year-old woman who was seen at the neurology clinic 10 days after her last cesarean section with diplopia and trouble swallowing liquids and solids for the previous 3 months. On examination she had slurred speech, bilateral palpebral ptosis, and mild droop of her shoulders. An arterial blood sample showed a PCO2 of 50 mmHg and a PO2 of 70 mmHg. The tensilon test was positive, Intravenous methylprednisolone and immunoglobulin and oral pyridostigmine effectively relieved her myasthenic signs and symptoms. Five assays for acetylcholine or anti-striational antibodies in her serum were negative. A test for muscle-specific tyrosine kinase antibody was positive. In 10-20% of patients with myasthenia gravis no antibodies to acetylcholine receptors are detectable. Forty percent of this group has an antibody to muscle-specific tyrosine kinase.
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Anticuerpos/sangre , Miastenia Gravis/sangre , Miastenia Gravis/inmunología , Complicaciones del Embarazo/sangre , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Femenino , Humanos , Embarazo , Adulto JovenRESUMEN
Introdução: A miastenia gravis (MG) adquirida é uma desordem neuromuscular, que dificulta a transmissão do impulso nervoso e provoca fadiga e fraqueza flutuantes na musculatura ocular, facial, dos membros e respiratória.Casuística: Foram avaliados 51 pacientes com MG, 38 submetidos a tratamento conservador e 13 timectomizados. Métodos: Os instrumentos de QV como Whoqol, qualidade de vida relacionada à saúde (QVRS) SF-36, e depressão ( BDI) foram utilizados.Estatística: Na análise univariada :Wilcoxon, U-Mann-Whitney, Fisher e razão de chance; e na análise multivariada a interação de múltiplos fatores.Resultados: Não houve diferenças significantes entre as terapêuticas em relação aos aspectos clínicos, QV, QVRS e Depressão, através da análise univariada / bem estar nos pacientes...
Introduction: Myasthenia gravis (MG) is an immune mediated neuromuscular disease and orders in nervous impulse transmission. The disease´s clinical characteristics include fatigability and fluctuating weakness of voluntary muscles. Objective: To evaluate the influence of conservative treatment and thymectomy on Qol and clinical response of myasthenic patients.Subjects: Fifty-one myasthenic patients were chosen ; 38 were submitted to conservative therapy and 13 to thymectomy. Methods: Quantitative Qol tools such as Whoqol, SF-36 and BDI were employed to evaluate Qol, HRQol and depression.Statistics: Univariate analysis: Wilcoxon, U-Mann Whitney Fisher tests, Chi-Square.Discriminant analysis was used to analyze the interation of multiple factors.Results: There was no differences between therapeutics groups concerning clinical progress, QoL, HRQoL and depression.The evaluation of multiple parameters pointed to a strong and positive influence of thymectomy in the recovery of the patients...
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Masculino , Femenino , Adulto , Persona de Mediana Edad , Humanos , Miastenia Gravis/terapia , Calidad de Vida , Conductas Terapéuticas Homeopáticas , Depresión , Miastenia Gravis/cirugía , Miastenia Gravis/inmunología , Miastenia Gravis/psicología , Perfil de Impacto de Enfermedad , TimectomíaRESUMEN
OBJECTIVES: We compared the outcome of thymectomy for myasthenia gravis (MG) in two healthcare systems. In Nottingham, UK, thymectomy is performed for thymic enlargement and considered in acetylcholine receptor (AchR) antibody positive patients. In Santiago, Cuba, thymectomy is considered in all generalised MG patients irrespective of their radiological findings or AchR antibodies. METHOD: 22 MG patients in Nottingham and 75 in Santiago who had a thymectomy were identified and their notes reviewed. We compared the median age, stage of disease, thymic histology and clinical outcome at two years post-thymectomy. RESULTS: The median ages for the Cuban and Nottingham patients were 25 and 35 years respectively. The median stage of disease was IIa by Osserman's classification in both. In Nottingham, 59% (13/22) showed an improvement compared with 88 % (66/75) in Santiago (p < 0.01). There were significantly more cases of thymoma in Nottingham whereas thymic hyperplasia and atrophy were a more frequent finding in Cuban patients. The majority of cases who improved post-thymectomy had thymic hyperplasia on histology in both Nottingham (46%) and Cuban (61%) patients. CONCLUSION: Selecting MG patients based on thymic enlargement alone or AchR antibody positivity may be inadequate and thymectomy should perhaps be considered in all patients with generalised myasthenia.
Asunto(s)
Miastenia Gravis/diagnóstico , Miastenia Gravis/patología , Miastenia Gravis/cirugía , Timectomía , Adulto , Factores de Edad , Atrofia , Autoanticuerpos/análisis , Cuba , Femenino , Estudios de Seguimiento , Humanos , Hiperplasia/patología , Masculino , Miastenia Gravis/complicaciones , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , Estudios Retrospectivos , Estadísticas no Paramétricas , Timoma/complicaciones , Timo/patología , Neoplasias del Timo/complicaciones , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Reino UnidoRESUMEN
La miastenia gravis corresponde a una patología auto inmune que se presenta en todas las edades. Tiene una frecuencia general de 10 a 20 por 100 000 individuos y aproximadamente un 15 por ciento corresponde a niños. Se caracteriza por la presencia de debilidad muscular y fatiga fácil secundaria a una alteración de la transmisión sináptica neuromuscular. Su patogenia se basa en la presencia de anticuerpos antireceptor de acetilcolina que generan el bloqueo y destrucción de los receptores de acetilcolina de la unión neuromuscular. Estos anticuerpos al ser pesquisados en un paciente con clínica sugerente confirman el diagnóstico. A pesar del conocimiento actual de la enfermedad su tratamiento aún es controversial existiendo distintas alternativas. En la última década han existido avances en la descripción de mecanismos fisiopatológicos involucrados en la miastenia gravis y asimismo nuevas opciones terapéuticas. El objetivo de esta revisión fue actualizar el conocimiento de la miastenis gravis en pediatría principalmente en las áreas de diagnóstico y tratamiento. Se realizó una revisión en las bases de datos Cochrane, Medline y Doyma de los últimos 10 años. Los resultados muestran descripciones moleculares de la patología, experiencias de la timectomía como tratamiento en niños e investigaciones en el manejo inmunológico de la enfermedad.
Asunto(s)
Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Miastenia Gravis/terapia , Enfermedades Autoinmunes , Inmunosupresores/uso terapéutico , Debilidad Muscular/etiología , Electromiografía , Inhibidores de la Colinesterasa , Inhibidores de la Colinesterasa/uso terapéutico , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , TimectomíaRESUMEN
Cytokines, such as interferons (IFN), underlie many immunological functions and are increasingly implicated in disease-related symptoms and pathology. In order to study the potential roles of IFN alpha and its antagonists in autoimmune phenomena, the sera from 89 patients (aged 15-95 years, 65 females) diagnosed as having myasthenia gravis (MG) (2 months to 34 years duration) were tested for the presence of natural anti-IFN alpha-2b auto-antibodies. Sera were screened for anti-IFN alpha-2b by a sandwich-type enzyme immunoassay system. Ten (11.2%) and 6 (6.7%) sera were identified that contained positive-competing and non-competing anti-IFN alpha-2b auto-antibodies, respectively. The MG sera were further analyzed by immunobloting against reduced IFN alpha-2b and for neutralizing anti-IFN alpha activity in an antiviral assay cells system. From tested EIA positive-competing sera, 5 were shown to be positive by immunoblot and 6 sera were found to contain neutralizing anti-IFN alpha-2b. Four of the 6 neutralizing anti-IFN alpha-2b sera came from patients with thymoma-associated MG. The sera were studied for linear epitope recognition on the IFN alpha-2b molecule by a solid phase binding assay, in which overlapping peptides homologous with the entire IFN alpha-2b sequence were separately synthesized on a nitrocellulose sheet. Peptides number 2 (residues 8-21), 3 (15-28), 6 (33-46), 10 (63-76), 15 (98-112), and 21 (141-154) were immunoreactive. Peptide 21 was apparently associated with antiviral activity, although peptide 21 has not been previously described as an immunogenic determinant on the IFN alpha-2b molecule. These results indicate that neutralizing anti-IFN alpha-2b is often present in MG, particularly in cases of thymoma-associated MG, and recognize a variety of epitopes on the IFN alpha-2b molecule, including those involved in its biological activity. Two groups of IFN epitopes were described associated with patient's age but not with diseases evolution.
Asunto(s)
Anticuerpos/inmunología , Mapeo Epitopo , Epítopos/inmunología , Interferón-alfa/inmunología , Miastenia Gravis/inmunología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Immunoblotting , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Multidrug resistance (MDR) mechanisms have been widely studied in cancer. Among them, P-glycoprotein (P-gp) overfunction has been associated with resistance to several antineoplastic agents. The physiological role of P-gp involves hormone and metabolite secretion, bacterial product detoxification, and transport of several drugs to the extracellular space, thus inhibiting their toxic or therapeutic effects. The study of MDR-1 in diseases of autoimmune origin has just recently emerged. Corticosteroids remain the mainstay therapy for autoimmune diseases. As prednisone (PDN) is transported by P-gp, the aim of this study was to evaluate the P-gp function in lymphocytes from myasthenia gravis (MG) patients. Thirty MG patients and 25 healthy controls were studied. Peripheral blood mononuclear cells were isolated by gradient centrifugation and incubated with daunorubicin (DNR) (a fluorescent drug extruded by P-gp). Functional activity of P-gp was analyzed by flow cytometry. Results were expressed as percentage of gated lymphocytes able to efflux DNR. Overall, MG patients showed increased numbers of lymphocytes with functional P-gp activity when compared with controls (x = 4.92 +/- 5.26% vs. x = 0.7 +/- 0.48%, respectively) (P < 0.0001). When patients were classified as responders (n = 21) or refractory (n = 9) to treatment, the latter group exhibited higher values of functional P-gp (x = 10.18 +/- 6.39%) when compared to the responder group (x = 2.66 +/- 2.45%) (P = 0.0076). These data suggest, on the one hand, that drug resistance may be induced by long-term treatment or by high PDN doses and, on the other, emphasize the need for the study of P-gp antagonists in order to improve the current therapeutical schemes for the treatment of MG.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/sangre , Linfocitos/metabolismo , Miastenia Gravis/metabolismo , Adolescente , Adulto , Azatioprina/uso terapéutico , Daunorrubicina/farmacología , Femenino , Citometría de Flujo , Colorantes Fluorescentes/farmacología , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inmunología , Prednisolona/uso terapéuticoRESUMEN
OBJECTIVE: To identify the response to thymectomy in patients with seronegative and seropositive myasthenia gravis (SPMG). We analyzed the associated diseases, thymus histology, and the severity of symptoms between the two groups. MATERIAL AND METHODS - DESIGN: Descriptive, comparative. STUDY UNITS: Fourteen patients with seronegative myasthenia gravis (SNMG) and 57 patients with SPMG who had a thymectomy between 1987 and 1997, with at least 3 years of follow-up. The patients were divided into four groups; (1) Remission, (2) Improvement, (3) No change and (4) Deterioration. RESULTS: Fourteen patients (20%) were seronegative and 57 were seropositive (80%). In the group of patients with SNMG, three patients were in remission (21%), five with improvement (36%), five with no change (36%) and one with worsening (7%). In the group of patients with SPMG, 12 were in remission (21%), 17 with improvement (30%), 25 with no change (44%) and three (5%) with worsening. The patients with SNMG were older, with less associated diseases and with a lower frequency of thymomas. CONCLUSIONS: The response to thymectomy was similar between the two groups. It has been suggested that seronegative patients have a better prognosis, but our results show no differences.
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Autoanticuerpos/sangre , Miastenia Gravis/cirugía , Complicaciones Posoperatorias/diagnóstico , Receptores Colinérgicos/inmunología , Timectomía , Timoma/cirugía , Hiperplasia del Timo/cirugía , Neoplasias del Timo/cirugía , Adulto , Progresión de la Enfermedad , Edrofonio , Electromiografía , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Miastenia Gravis/inmunología , Miastenia Gravis/patología , Examen Neurológico , Timoma/inmunología , Timoma/patología , Hiperplasia del Timo/inmunología , Hiperplasia del Timo/patología , Neoplasias del Timo/inmunología , Neoplasias del Timo/patología , Resultado del TratamientoRESUMEN
Se realizó un estudio observacional descriptivo con el objetivo de describir el comportamiento de algunos factores inmunológicos en la Miastenia Grave. Se trabajó con una muestra de 50 pacientes miasténicos atendidos en el Hospital Provincial Manuel Ascunce Domenech de Camagüey durante los años 1995-2001. Los estudios inmunológicos se realizaron en La Habana, con previa coordinación entre nuestro Hospital y el Instituto de Neurología y el Hospital Hermanos Ameijeiras. El estudio reveló un predominio del sexo femenino (64 por ciento) y del tipo Miasténico II-B (28por ciento); los principales autoanticuerpos identificados fueron los antimúsculos estriado (46por ciento) , cardíaco ( 44 por ciento) y liso ( 42 por ciento), mientras que, los HLA más frecuentes fueron el DRW3 ( 22 por ciento), B 27 (22por ciento) y DR3 (16por ciento). El 10 por ciento de los pacientes presentó una enfermedad asociada siendo la más frecuente el lupus eritematoso sistémico (6 por ciento). La hiperplasia tímica fue el hallazgo más frecuente tanto tomográfico como histológico(AU)
Asunto(s)
Humanos , Masculino , Femenino , Miastenia Gravis/inmunologíaRESUMEN
Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 percent of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1). Eleven patients (61 percent) presented moderate or severe generalized disease and 4 (22 percent) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47 percent) out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6 percent (9 out of 11 tested) and the levels had no relation to clinical severity. Nine out of 16 patients (56 percent) worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia). Three patients (75 percent) improved markedly after thymectomy and one (25 percent) worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Miastenia Gravis/diagnóstico , Miastenia Gravis/cirugía , Edad de Inicio , Inhibidores de la Colinesterasa , Estudios de Seguimiento , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inmunología , Prednisona/uso terapéutico , Bromuro de Piridostigmina/uso terapéutico , Receptores Colinérgicos/sangre , Receptores Colinérgicos/inmunología , Timectomía , Tomografía Computarizada por Rayos XRESUMEN
Myasthenia gravis is a neuromuscular, autoimmune, and acquired disturbance characterized by weakness and fatigue of skeletal muscles. During the past two decades, remarkable progress has been made in the understanding of myasthenia gravis, and the new knowledge has been applied directly to the clinical diagnosis and treatment of this formerly severe disease. Myasthenia gravis is undoubtedly the most thoroughly understood of all human autoimmune diseases and has served as a model for the elucidation of mechanisms underlying other autoimmune disorders. In this review we mention the most important physiopathological aspects and its application in the clinic practice.
Asunto(s)
Miastenia Gravis/etiología , Humanos , Miastenia Gravis/inmunología , Unión Neuromuscular , Receptores ColinérgicosRESUMEN
Estudio retrospectivo de 217 pacientes con miastenia gravis, timectomizados. De los pacientes de la serie, 189 (87,1 por ciento) presentaron alguna alteración histológica y en 28 (12,9 por ciento) se encontró un timo sin anormalidades patológicas. La hiperplasia tímica fue la alteración más frecuente (73,7 por ciento), en tanto que la presencia de timoma fue menos común (13,4 por ciento). Las principales características clínicas halladas en el grupo con hiperplasia fueron la presentación de la enfermedad por debajo de los 30 años, mercado predominio del sexo femenino y baja frecuencia de complicaciones de la timectomía. En la mayoría de los casos con timoma, el inicio de la miastenia ocurrió después de la cuarta década. En estos casos hallamos formas más severas de la miastenia, mayor número de complicaciones de la timectomía y más alta mortalidad posoperatoria. También se destacan los beneficios de la timectomía sobre otros tratamientos(AU)