RESUMO
BACKGROUND: Myasthenia gravis (MG) is a neuromuscular disorder characterized by an autoimmune defect in the neuromuscular junction. In most patients, the autoimmune attack is mediated by antibodies against the acetylcholine receptor (AChR) on the postsynaptic membrane. Deficient immunoregulation, including regulatory T cells, is consistently observed. Extracorporeal photopheresis (ECP) leads to the induction of regulatory T cells that mediate immunologic tolerance in autoimmune diseases; however, the data regarding MG are very limited. CASE REPORT: Here, we report a patient who, during ongoing ECP therapy for his severe, refractory, chronic graft-versus-host disease (cGVHD), developed MG, although he responded very well to ECP, as indicated by the lowering of his chronic cGVHD severity grade to moderate. RESULTS: Despite receiving ECP, our patient developed MG, which was resistant to treatment and required intensive care unit support. CONCLUSIONS: Close surveillance is required when ECP is planned as one of the treatment alternatives in myasthenia gravis that develop in cGVHD.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Miastenia Gravis/prevenção & controle , Fotoferese , Doença Crônica , Doença Enxerto-Hospedeiro/complicações , Humanos , Masculino , Miastenia Gravis/etiologia , Miastenia Gravis/terapiaRESUMO
This study aims to observe the effect of natural killer T (NKT) cell activation on experimental autoimmune myasthenia gravis (EAMG) model by injecting mice with α-GalCer in enterocoelia at different times, thus to provide a new therapy for EAMG. EAMG animal model of C57BL/6 mice was established and the mice were injected with α-GalCer irritant in enterocoelia. Vα14 NKT NKT cells were then activated through the transfer of CD1d. This paper discusses the effect of NKT cell activation on EAMG at different times by observing the variation of weight, clinical performance and relevant immunity indexes of mice. In C57BL/6 mice, the EAMG incidence rate of the Vehicle Group was 90%, the average onset duration was 37 ± 6 days; The incidence rate of α-GalCer prevention group was 30%;, the average onset duration was 51 ± 9 days. The forward immunization of α-GalCer activates NKT and protects C57BL/6 mice from the occurrence of EAMG, which provides basis for prevention and treatment of EAMG and other autoimmune diseases.
Assuntos
Galactosilceramidas/imunologia , Células Matadoras Naturais/imunologia , Miastenia Gravis/imunologia , Animais , Peso Corporal/imunologia , Modelos Animais de Doenças , Feminino , Galactosilceramidas/farmacologia , Imunoglobulina G/sangue , Ativação Linfocitária/imunologia , Camundongos Endogâmicos C57BL , Miastenia Gravis/prevenção & controle , Receptores Colinérgicos/imunologiaRESUMO
Corticosteroids may produce a paradoxical worsening of myasthenia gravis (MG) symptoms within the first weeks of treatment. We therefore wanted to assess the hypothesis that a prior infusion of intravenous immunoglobulin (IVIG) may have a protective effect. Our primary objectives were to show that the coadministration of immunoglobulins and glucocorticoids is safe and effective for controlling myasthenic symptoms, and to compare the exacerbation rate with this approach and historical practice without IVIG. We recruited 45 patients with generalized MG who required corticosteroids for the first time and we gave all IVIG before starting the full doses of prednisone. Monitoring was performed with validated scales, questionnaires, and blood tests over a 6-week period. Only 4.4% had severe adverse effects related to IVIG and 86.7% improved clinically. Notably, only 2.2% had a paradoxical symptom exacerbation in the first weeks of starting prednisone, which was statistically lower than the 42% reported in a historical series. We conclude that adjuvant therapy with IVIG when starting prednisone for the first time in patients with generalized MG is safe and effective. Given that the rate of paradoxical worsening was lower than that previously reported, the addition of IVIG may have a protective effect against such exacerbations.
Assuntos
Imunoglobulinas Intravenosas/farmacologia , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/prevenção & controle , Prednisona/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
T cell tolerization prevents and improves T cell-mediated experimental autoimmune diseases. We investigated here whether similar approaches could be used for antibody (Ab)-mediated autoimmune diseases. Myasthenia gravis, caused by IgG Ab against muscle acetylcholine receptor (AChR), is perhaps the best characterized of them. We used an animal model, experimental myasthenia gravis induced in C57Bl/6 mice by immunization with Torpedo acetylcholine receptor (TAChR), to demonstrate that nasal administration of synthetic sequences of the TAChR alpha-subunit- forming epitopes recognized by anti-TAChR CD4+ T helper cells (residues alpha150-169, alpha181-200, and alpha360-378), given before and during immunization with TAChR, causes decreased CD4+ responsiveness to those epitopes and to TAChR, reduced synthesis of anti-TAChR Ab, and prevented experimental myasthenia gravis. These effects were not induced by nasal administration of synthetic epitopes of diphtheria toxin. Secretion of IL-2, IL-4, and IL-10 by spleen T cells from TAChR immunized mice, in response to challenge with TAChR in vitro, indicated that in sham-tolerized mice only Th1 cells responded to TAChR, while peptide-treated mice had also an AChR-specific Th2 response. The TAChR peptide treatment induced also in vitro anergy to the TAChR of the spleen T cells, which was reversed by IL-2.
Assuntos
Epitopos de Linfócito T/imunologia , Miastenia Gravis/prevenção & controle , Receptores Colinérgicos/imunologia , Vacinas Sintéticas/imunologia , Administração Intranasal , Animais , Anticorpos/imunologia , Linfócitos T CD4-Positivos/imunologia , Toxina Diftérica/síntese química , Toxina Diftérica/imunologia , Modelos Animais de Doenças , Humanos , Imunização , Interleucina-2/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Miastenia Gravis/imunologia , Peptídeos/síntese química , Peptídeos/imunologia , Sistema Respiratório/metabolismo , Baço/citologia , Células Th2/imunologia , Torpedo , Vacinas Sintéticas/administração & dosagemRESUMO
The mucosal administration of the native antigen or peptide fragments corresponding to immunodominant regions is effective in preventing or treating several T cell-dependent models of autoimmune disease. No data are yet available on oral tolerance with immunodominant T-cell peptides in experimental autoimmune myasthenia gravis (EAMG), an animal model of B cell-dependent disease. We report that oral administration of the T-cell epitope alpha146-162 of the Torpedo californica acetylcholine receptor (TAChR) alpha-subunit suppressed T-cell responses to AChR and ameliorated the disease in C57Bl/6 (B6) mice. Protection from EAMG was associated with reduced serum Ab's to mouse AChR and reduced AChR loss in muscle. The effect of Talpha146-162 feeding was specific; treatment with a control peptide did not affect EAMG manifestations. The protective effect induced by peptide Talpha146-162 was mediated by reduced production of IFN-gamma, IL-2, and IL-10 by TAChR-reactive cells, suggesting T-cell anergy. TGF-beta-secreting Th3 cells did not seem to be involved in tolerance induction. We therefore demonstrate that feeding a single immunodominant epitope can prevent an Ab-mediated experimental model of autoimmune disease.
Assuntos
Citocinas/metabolismo , Epitopos de Linfócito T/administração & dosagem , Miastenia Gravis/prevenção & controle , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Regulação para Baixo , Epitopos de Linfócito T/farmacologia , Camundongos , Miastenia Gravis/imunologia , Peptídeos/farmacologia , Receptores Colinérgicos/imunologia , Células Th1/imunologia , Células Th2/imunologia , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta/genéticaRESUMO
Myasthenia gravis (MG) is a disabling autoimmune disease caused by autoantibodies (auto-Abs) against the self-acetylcholine receptor (AChR). Although a great deal of information is known about the molecular and cellular parameters of the disease, its initial trigger, however, is not known. To study the possibility of the involvement of microbial antigens that mimic AChR in triggering MG, we have searched the microbial proteins in the data bank for regions that are similar in structure to the regions of human (h) AChR alpha chain recognized by auto-Abs in MG patients. Hundreds of candidate structures on a large number of bacterial and viral proteins were identified. To test the feasibility of the idea, we synthesized four microbial regions similar to each of the major autodeterminants of hAChR (alpha12-27, alpha111-126, alpha122-138, alpha182-198) and investigated their ability to bind auto-Abs in MG and normal sera controls. It was found that MG sera potentially recognized a significant number of these microbial regions. The results indicate that in some MG cases, immune responses to microbial antigens may cross-react with self-antigen (in this case hAChR) and could constitute initial triggers of the disease. Although anti-AChR Abs directly contribute to the degradation of AChR at the neuromuscular junctions, autoreactive T cells provide help to B cells that synthesize anti-AChR auto-Abs. To cause MG, T cells must recognize the pathogenic epitopes in the context of MHC class II molecules related to MG. The ability to regulate AChR presentation (hence AChR-reactive T-cell activation) could form the basis of an effective strategy for the control of autoimmunity in MG by selectively inhibiting the function of the Ir gene loci linked to disease susceptibility. An animal model of MG (experimental autoimmune MG, EAMG) can be induced in C57BL/6 (B6, H-2b) mice by immunization with Torpedo californica (t) AChR. A mutant mouse of B6, B6.C-H-2bm12 (bm12), which has three amino acid changes (at residues 67, 70, and 71) in the I-A beta(b) subunit, is resistant to EAMG development. Recently, we showed that region 62-76 of I-A beta(b), which contains the above residues, is involved in the binding to a pathogenic T-cell epitope within peptide t alpha146-162. We have prepared several monoclonal antibodies (mAbs) against peptide I-A beta(b)62-76, which are highly cross-reactive with I-A(b) molecules. These mAbs inhibited in vitro the proliferation of disease-related T cells of B6 specific to tAChR peptide t alpha146-162. Passive transfer of these mAbs suppressed the occurrence of clinical EAMG, which was accompanied by lower T-cell and Ab responses to tAChR. The results indicated that blocking disease-related MHC by targeting a disease-associated region on MHC molecules could be an effective, straightforward, and feasible strategy for immunointervention in MG.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Apresentação de Antígeno , Epitopos de Linfócito T , Antígenos de Histocompatibilidade Classe II/imunologia , Miastenia Gravis/etiologia , Fragmentos de Peptídeos/imunologia , Receptores Colinérgicos/imunologia , Sequência de Aminoácidos , Animais , Autoanticorpos/imunologia , Linfócitos B/imunologia , Humanos , Ativação Linfocitária , Dados de Sequência Molecular , Miastenia Gravis/imunologia , Miastenia Gravis/prevenção & controleRESUMO
OBJECTIVE: A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. METHODS: We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. RESULTS: Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. CONCLUSIONS: Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.
Assuntos
Miastenia Gravis/etiologia , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/prevenção & controle , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Timectomia/métodos , Timoma/complicações , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/patologiaRESUMO
Experimental autoimmune myasthenia gravis (EAMG), which to some extent represents an experimental counterpart of human myasthenia gravis, can be induced by inoculation of various animal species and strains with acetylcholine receptor (AChR). The oral administration of Torpedo AChR to Lewis rats prior to immunization with Torpedo AChR and complete Freund's adjuvant resulted in prevention or delay in the onset of EAMG. Levels of anti-Torpedo AChR antibodies in serum measured by radioimmunoassay were lower in orally tolerant compared to control animals. The model might have a relevance for studying the pathogenesis and immunotherapy of human myasthenia gravis.
Assuntos
Miastenia Gravis/prevenção & controle , Receptores Colinérgicos/imunologia , Administração Oral , Animais , Autoanticorpos/sangue , Feminino , Tolerância Imunológica , Imunização , Miastenia Gravis/imunologia , Ratos , Ratos Endogâmicos Lew , TorpedoRESUMO
We have prepared monoclonal antibodies (mAbs) against an antigen-binding region of I-A, region 62-76 of I-Abeta(b), which is involved in the T-cell participation in the pathogenesis of EAMG. The mAbs reacted with its parent molecules and inhibited the proliferation of disease-related T-cells. Passive transfer of these mAbs suppressed the occurrence of clinical EAMG, which was accompanied by decreased T-cell and Ab responses to tAChR. The results indicated that blocking the function of disease-related MHC by targeting a disease-associated region on MHC molecules could be an effective, straightforward and feasible strategy for immunointervention in MG.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Apresentação de Antígeno , Epitopos de Linfócito T , Antígenos de Histocompatibilidade Classe II/imunologia , Miastenia Gravis/prevenção & controle , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Formação de Anticorpos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Receptores Colinérgicos/imunologiaRESUMO
Oral administration of acetylcholine receptor (AChR) or myelin basic protein (MBP) to Lewis rat prior to immunization with AChr or MBP and complete Freund's adjuvant (CFA) has previously been shown to prevent or delay the onset of experimental autoimmune myasthenia gravis (EAMG) or experimental allergic encephalomyelitis (EAE), which represent animal models of myasthenia gravis and multiple sclerosis, respectively. Here we show that Lewis rats immunized with AChr+MBP+CFA developed both signs of muscular weakness seen in EAMG and paresis characteristic for EAE. This disease was associated with high levels of anti-AChR and anti-MBP antibody secreting cells and of AChR- and MBP-reactive INF-gamma secreting Th1-like cells in lymph nodes. The diseased rats also showed upregulation of AChR- and MBP-induced mRNA expression of IFN-gamma in lymph node cells. Oral tolerization with AChR and MBP in combination prior to immunization with AChR+MBP+CFA alleviated clinical disease as well as AChR- and MBP-specific B cell node cells. The results implicate that oral tolerization simultaneously to more than one autoimmune disease-related autoantigen is feasible, and that suppression of autoantigen-induced IFN-gamma and augmentation of TGF-beta are pivotal in tolerance induction.
Assuntos
Encefalomielite Autoimune Experimental/prevenção & controle , Tolerância Imunológica , Miastenia Gravis/prevenção & controle , Proteína Básica da Mielina/imunologia , Receptores Colinérgicos/imunologia , Administração Oral , Animais , Feminino , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-4/genética , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos Lew , Fator de Crescimento Transformador beta/genéticaRESUMO
Experimental autoimmune myasthenia gravis (EAMG) is a well established animal model, which can be induced in various animal species and strains with acetylcholine receptor (AChR) and represents an experimental counterpart of human myasthenia gravis (MG). Current immunotherapies of both EAMG and MG are non-specific and limited by their toxicity. Tolerance to EAMG has been achieved by oral administration of milligram quantities of Torpedo AChR. In the present report we demonstrate that nasal administration of microgram doses of Torpedo AChR to female Lewis rats prior to immunization with Torpedo AChR and complete Freund's adjuvant resulted in the prevention of subsequently induced EAMG, the suppression of serum anti-AChR antibody levels, the decrease of delayed-type hypersensitivity responses to AChR, as well as the suppression of AChR-specific immunoglobulin G-secreting cells, AChR-reactive interferon-gamma-secreting cells and T cell proliferation in peripheral lymphoid organs, particularly in popliteal and inguinal lymph nodes regional to immunization. We conclude that clinical signs of EAMG can be efficiently prevented by nasal administration of AChR in parallel with the downregulation of both B and T cell responses specific to AChR.
Assuntos
Interferon gama/biossíntese , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Administração Intranasal , Animais , Concanavalina A , Órgão Elétrico/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade Tardia , Imunoglobulina G/biossíntese , Ativação Linfocitária , Miastenia Gravis/fisiopatologia , Miastenia Gravis/prevenção & controle , Proteína Básica da Mielina/imunologia , Ratos , Ratos Endogâmicos Lew , Receptores Colinérgicos/isolamento & purificação , Fatores de Tempo , TorpedoRESUMO
Immunization with acetylcholine receptor (AChR) causes experimental myasthenia gravis (EMG). The s.c. administration to C57B1/6 mice of synthetic AChR CD4+ epitopes, before and during AChR immunization, reduced the epitope-specific CD4+ responses and the anti-AChR Ab synthesis, and prevented EMG. The s.c. administration of solubilized AChR had effects similar to those of peptide treatment. Sham-tolerized mice had only Th1 anti-AChR cells, whereas peptide-treated mice had also Th2 cells, and Th2-induced anti-peptide Ab. Established EMG was not affected by s.c. peptide treatment, whereas it worsened after s.c. administration of solubilized AChR.
Assuntos
Epitopos/imunologia , Miastenia Gravis/imunologia , Miastenia Gravis/prevenção & controle , Receptores Colinérgicos/imunologia , Animais , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Modelos Animais de Doenças , Epitopos/farmacologia , Tolerância Imunológica/imunologia , Imunização , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/farmacologia , Solubilidade , Células Th2/imunologia , TorpedoRESUMO
Peptide p259-271 of the human acetylcholine receptor alpha-subunit, preferentially stimulates T cells of patients with myasthenia gravis (MG) and is an immunodominant epitope for T cells of BALB/c mice. A p259-271 specific T cell line of BALB/c origin was established and was shown to induce experimental MG in naive mice. Seven analogs of p259-271 were synthesized, and two of them were found to inhibit the p259-271 specific proliferative responses of the line and of p259-271 primed lymph node cells. Moreover, the most efficient inhibitor, analog 262Lys, prevented the MG related manifestations in mice inoculated with the line, and might be of potential value for the treatment of MG.
Assuntos
Doenças Autoimunes/prevenção & controle , Miastenia Gravis/etiologia , Miastenia Gravis/prevenção & controle , Fragmentos de Peptídeos/genética , Receptores Colinérgicos/genética , Linfócitos T/fisiologia , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Feminino , Humanos , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Immunization with acetylcholine receptor (AChR) causes experimental myasthenia gravis (EMG). We investigated EMG in interleukin (IL)-4 knock out B6 (KO) mice, that lack Th2 cells. EMG was more frequent in KO than in wild type B6 mice. KO and B6 mice developed similar amounts of anti-AChR antibodies. They were IgG2a and IgG2b in KO mice, IgG1 and IgG2b in B6 mice. CD4+ cells from KO and B6 mice recognized the same AChR epitopes. Nasal administration of synthetic AChR CD4+ epitopes reduced antibody synthesis and prevented EMG in B6, not in KO mice. Thus, Th2 cells may have protective functions in EMG.
Assuntos
Antígenos CD4/farmacologia , Interleucina-4/genética , Miastenia Gravis/imunologia , Miastenia Gravis/prevenção & controle , Receptores Colinérgicos/imunologia , Administração Intranasal , Animais , Autoanticorpos/imunologia , Autoanticorpos/farmacologia , Doenças Autoimunes/imunologia , Bungarotoxinas/farmacologia , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Antígenos CD8/metabolismo , Proteínas do Sistema Complemento/análise , Epitopos/imunologia , Imunoglobulina G/análise , Interleucina-4/deficiência , Interleucina-4/imunologia , Camundongos , Camundongos Knockout , Mutagênese/imunologia , Junção Neuromuscular/química , Junção Neuromuscular/imunologia , Baço/citologia , Baço/imunologia , Células Th1/química , Células Th1/imunologia , Células Th2/química , Células Th2/imunologia , TorpedoRESUMO
Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides T alpha 73-89, T alpha 351-368, T delta 354-367 and H alpha 351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Especificidade de Anticorpos/efeitos dos fármacos , Miastenia Gravis/imunologia , Fragmentos de Peptídeos/imunologia , Receptores Colinérgicos/imunologia , Sequência de Aminoácidos , Animais , Modelos Animais de Doenças , Epitopos/imunologia , Imunização Passiva , Dados de Sequência Molecular , Miastenia Gravis/prevenção & controle , Radioimunoensaio , TorpedoRESUMO
Maternal myasthenia gravis has been associated with the presence of neonatal myasthenia and sometimes fatal congenital anomalies. As a result, antenatal therapy directed at fetal sequelae may be indicated. We present the case of a pregnant myasthenic woman whose two previous pregnancies had ended in neonatal deaths from fetal deformations that were presumably due to maternal myasthenia. Serial plasmaphereses and oral prednisone therapy were used in an attempt to depress maternal anti-acetylcholine receptor antibody titers. As anti-acetylcholine receptor antibody titers fell, fetal breathing movements became apparent by ultrasound, and as these titers rose, no fetal breathing movements were apparent. Our patient delivered an infant with transient neonatal myasthenia but normal pulmonary development and no deformations. We suggest that the therapy given may have improved the outcome of this pregnancy compared with her two previous pregnancies.
Assuntos
Miastenia Gravis/terapia , Plasmaferese , Prednisona/uso terapêutico , Complicações na Gravidez/terapia , Administração Oral , Adulto , Anticorpos Anti-Idiotípicos/imunologia , Feminino , Doenças Fetais/prevenção & controle , Humanos , Recém-Nascido , Miastenia Gravis/imunologia , Miastenia Gravis/prevenção & controle , Prednisona/administração & dosagem , Gravidez , Complicações na Gravidez/imunologia , Receptores Colinérgicos/imunologiaRESUMO
Oral administration of acetylcholine receptor (AChR) to Lewis rats prior to myasthenogenic immunization with AChR and complete Freund's adjuvant (CFA) results in the prevention of experimental autoimmune myasthenia gravis (EAMG), and decreased serum levels of anti-AChR antibodies. Using an ELISPOT assay, we have now determined numbers of cells in the popliteal, inguinal and mesenteric lymph nodes, spleen and thymus secreting anti-AChR IgG antibodies. Except for mesenteric lymph nodes, a marked diminution of such cells was detected in these lymphoid organs in rats orally tolerized with AChR compared to buffer-fed or vehicle-fed control rats with EAMG. Of note is that, after AChR feeding, the B cell response to AChR in thymus was diminished to the same low level as in CFA-injected, buffer-fed control rats. The relative affinity of serum anti-AChR IgG antibodies measured by KSCN-ELISA was lower in the orally tolerized rats compared to buffer-fed or vehicle-fed rats. The observations showed that oral administration of AChR, besides preventing clinical EAMG, also counteracts the development of AChR-specific B cells, especially those with high affinity antibody production, in most lymphoid organs.
Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Tolerância Imunológica , Tecido Linfoide/imunologia , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Administração Oral , Animais , Afinidade de Anticorpos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/prevenção & controle , Soluções Tampão , Encefalomielite Autoimune Experimental/imunologia , Feminino , Adjuvante de Freund , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Linfonodos/imunologia , Linfonodos/patologia , Tecido Linfoide/patologia , Miastenia Gravis/prevenção & controle , Proteína Básica da Mielina/toxicidade , Veículos Farmacêuticos , Ratos , Ratos Endogâmicos Lew , Timo/imunologia , Timo/patologia , TorpedoRESUMO
Fifty percent of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia, 90% within 3 years from the onset of ocular symptoms. This study was performed to determine whether treatment with oral prednisone initiated and completed within 2 years from the onset of ocular symptoms would affect the progression of ocular myasthenia to generalized myasthenia gravis (GMG). Fifty-six patients were included in this review, with 27 patients in the prednisone-treated group and 29 patients in the untreated group. The treated group was initiated on 60 mg of prednisone daily with a slow taper over 3-6 months. At 2 years, significantly fewer patients in the treated group (3 of 27) progressed to generalized myasthenia when compared to the untreated group (10 of 29) (chi(2), p=0.04). Our results suggest that the early use of steroids may decrease progression of ocular to generalized myasthenia gravis. The decision to use steroids should be considered early in the course of patients diagnosed with ocular myasthenia gravis. This study should be considered preliminary and a prospective trial is warranted to confirm our observations.
Assuntos
Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/prevenção & controle , Prednisona/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/fisiopatologia , Músculos Oculomotores/efeitos dos fármacos , Músculos Oculomotores/imunologia , Músculos Oculomotores/fisiopatologia , Brometo de Piridostigmina/uso terapêutico , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA) alleviated clinical signs of experimental autoimmune myasthenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via the nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multiphasic clinical picture with a combination of clinical signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by massive macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs. Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppressed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transforming growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate the possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans.