RÉSUMÉ
The intestinal microbiota plays a key role in the maintenance of human health. Alterations in this microbiota have been described in several autoimmune diseases, including nervous system diseases. Nevertheless, the information regarding neuromuscular conditions is still limited. In this study, we aimed at characterizing the intestinal microbiota composition in myasthenia gravis patients (MG). To this end fecal samples were taken from ten patients, with antibodies against the acetylcholine receptor, and ten age and sex matched controls from the same population (Asturias region, Spain). Fecal samples were submitted to microbiota analyses by 16S rRNA gene profiling, bifidobacterial ITS-region profiling and qPCR. The fecal levels of short chain fatty acids were determined by gas chromatography. MG patients were found to harbor lower relative proportions of Verrucomicrobiaceae and Bifidobacteriaceae, among others, and increased of the phylum Bacteroidetes and the family Desulfovibrionaceae. The increase of these latter microbial groups was also confirmed at quantitative level by qPCR. In contrast, no statistically significant differences were found between MG patients and the control group in the bifidobacterial population at the species level or in short chain fatty acids profiles. Our data indicates an altered fecal microbiota pattern in MG patients and point out at specific microbiota targets for intervention in this population.
Sujet(s)
Fèces/microbiologie , Myasthénie/microbiologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Bacteroidetes/génétique , Bacteroidetes/isolement et purification , Bifidobacterium/génétique , Bifidobacterium/isolement et purification , Desulfovibrionaceae/génétique , Desulfovibrionaceae/isolement et purification , Femelle , Microbiome gastro-intestinal , Humains , Mâle , Adulte d'âge moyen , ARN ribosomique 16S/génétique , Transcriptome , Verrucomicrobia/génétique , Verrucomicrobia/isolement et purificationRÉSUMÉ
Nineteen patients with bronchopulmonary infection and myasthenia gravis were enrolled in the study. The microbiological analysis of the specimens of phlegm and bronchial secretion revealed both grampositive and gramnegative bacteria. All the isolates were susceptible to the antibiotic used (cefoperazone/sulbactam). Intravenous immunoglobulins (IvIgs) were used to increase the treatment efficacy, to opsonize the infection foci and to decrease the hospitalization terms. The antibiotic therapy and simultaneous use of intravenous immunoglobulins provided higher clinical efficacy in 16 out of 19 patients (84.2%).
Sujet(s)
Antibactériens/usage thérapeutique , Bronchopneumonie/traitement médicamenteux , Céfopérazone/usage thérapeutique , Immunoglobulines par voie veineuse/usage thérapeutique , Myasthénie/traitement médicamenteux , Pneumopathie bactérienne/traitement médicamenteux , Sulbactam/usage thérapeutique , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Bronchopneumonie/complications , Bronchopneumonie/immunologie , Bronchopneumonie/microbiologie , Association de médicaments , Femelle , Bactéries à Gram négatif/effets des médicaments et des substances chimiques , Bactéries à Gram négatif/croissance et développement , Bactéries à Gram positif/effets des médicaments et des substances chimiques , Bactéries à Gram positif/croissance et développement , Humains , Mâle , Adulte d'âge moyen , Myasthénie/complications , Myasthénie/immunologie , Myasthénie/microbiologie , Pneumopathie bactérienne/complications , Pneumopathie bactérienne/immunologie , Pneumopathie bactérienne/microbiologie , Résultat thérapeutiqueRÉSUMÉ
INTRODUCTION: Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. METHODS: 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. RESULTS: Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p<0.001) with age throughout the study population, while titers of A-TET dropped only in the elderly (>60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in <40-years-old subjects, A-DIPHTH level was significantly (p=0.029) lower in SLE patients than in controls. CONCLUSIONS: Our findings suggest that the level of vaccine-induced immunity against diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population.
Sujet(s)
Vaccin diphtérie-tétanos-coqueluche/immunologie , Diphtérie/immunologie , Lupus érythémateux disséminé/immunologie , Myasthénie/immunologie , Tétanos/immunologie , Adulte , Sujet âgé , Anticorps antibactériens/immunologie , Production d'anticorps/immunologie , Études cas-témoins , Diphtérie/complications , Antitoxine diphtérique/immunologie , Anatoxine diphtérique/immunologie , Vaccin diphtérie-tétanos-coqueluche/administration et posologie , Femelle , Humains , Immunité humorale/immunologie , Immunoglobuline G/immunologie , Lupus érythémateux disséminé/microbiologie , Mâle , Adulte d'âge moyen , Myasthénie/microbiologie , Tétanos/complications , Anatoxine tétanique/immunologieRÉSUMÉ
Nocardiosis is increasingly being diagnosed because of a growing population of immunocompromised hosts and improvements in the detection of Nocardia species in clinical laboratories. Historically, sulphonamides have been the first-line therapy for the treatment of nocardiosis, but sulphonamides tend to have a high rate of drug allergy in clinical settings. In this report, we described a disseminated Nocardia farcinica infection that occurred in a patient with myasthenia gravis who suffered from multiple drug allergies and was successfully treated using linezolid. We undertook a review of the literature of previously reported cases of nocardiosis treated with linezolid. To date, only 15 cases of nocardiosis treated with linezolid have been published. All cases exhibited long-term tolerance of linezolid, and 14 of 15 cases showed either an improvement in or complete clearance of the infection. According to the literature review, linezolid is an attractive alternative to trimethoprim-sulfamethoxazole for the treatment of disseminated nocardiosis, despite limited clinical evidence to support this claim.
Sujet(s)
Acétamides/usage thérapeutique , Antibactériens/usage thérapeutique , Myasthénie/microbiologie , Infections à Nocardia/traitement médicamenteux , Nocardia/isolement et purification , Oxazolidinones/usage thérapeutique , Hypersensibilité médicamenteuse , Femelle , Humains , Linézolide , Adulte d'âge moyen , Infections à Nocardia/complicationsRÉSUMÉ
Foamy viruses are a group of retroviruses of complex structure which were thought to be non-pathogenic. The recent demonstration of neurological diseases in mice transgenic for human foamy virus (HFV) and the high prevalence of HFV sequences in Graves' disease question this idea. By PCR, we have detected HFV sequences with a non-random deletion in the bel1 transactivator gene in other autoimmune conditions. Sequence analysis revealed that this deleted area corresponds to the excision of a known intron in bet, one of HFV's regulatory genes. The same phenomenon was observed in both acute and chronic infections, in vitro or in vivo, although the deleted forms were distinctly more abundant in chronic states. The viral DNA containing the bel1 deletion is apparently part of an otherwise complete genome, strongly suggesting that this provirus derives from the reverse transcription of a spliced pregenomic RNA. Bel1-spliced provirus was shown to be defective when transfected into permissive cells. However, co-expression with the Bel1 transactivator led to functional trans-complementation and formation of viral particles. Splicing of the genome may be an important factor in HFV biology: genomes with the deletion may either interfere with wild-type virus expression or alter host cell functions through background expression of viral regulatory proteins.
Sujet(s)
Protéines de liaison à l'ADN/génétique , Virus défectifs/génétique , Provirus/génétique , Épissage des ARN , Protéines des retroviridae/génétique , Spumavirus/génétique , Transactivateurs/génétique , Maladie aigüe , Animaux , Séquence nucléotidique , Cellules cultivées , Maladie chronique , Protéines de liaison à l'ADN/isolement et purification , Technique d'immunofluorescence , Délétion de gène , Gènes viraux , Génome viral , Humains , Introns/génétique , Données de séquences moléculaires , Myasthénie/microbiologie , Réaction de polymérisation en chaîne , ARN messager/génétique , Lapins , Protéines des retroviridae/isolement et purification , Transactivateurs/isolement et purificationRÉSUMÉ
Using a simple method of long-term culture, it was possible to obtain B-like lymphoblastoid cell lines (LyCLs) from myasthenic thymuses. Successful cultures were carried out from 14 out of 15 hyperplastic thymuses and in 1 out of 3 myasthenic thymoma, whereas none of the 8 control thymuses, nor the 2 Myasthenia gravis-associated normally involuted thymuses, nor the Myasthenia gravis-associated lymphoma gave rise to LyCL. All the LyCLs secreted immunoglobulins (Ig), either IgG or IgM. None of these Ig reacted with acetylcholine receptor or with other antigens known to be often involved in autoimmune diseases. EBV antigens were found in all the LyCLs as well as in the corresponding donors at the time of thymectomy. HLA characterization of some LyCLs and the corresponding donors showed that class II MHC antigens were expressed normally or with mild differences. However, 86% of the LyCL tested did not express class I MHC antigens.
Sujet(s)
Lymphocytes B/immunologie , Myasthénie/immunologie , Thymus (glande)/immunologie , Lymphocytes B/microbiologie , Lymphocytes B/anatomopathologie , Lignée cellulaire , Techniques cytologiques , Épithélium/anatomopathologie , Antigènes HLA , Herpèsvirus humain de type 4/immunologie , Herpèsvirus humain de type 4/isolement et purification , Humains , Immunoglobuline G/biosynthèse , Immunoglobuline M/biosynthèse , Myasthénie/microbiologie , Myasthénie/anatomopathologie , Phénotype , Récepteurs cholinergiques/immunologie , Thymus (glande)/microbiologie , Thymus (glande)/anatomopathologieRÉSUMÉ
Thymectomy was carried out for treatment of myasthenia gravis in 27 unselected Chinese patients and thymoma was found in 13 of them. This 48% incidence of thymomas is two to three times greater than in Japanese and European patients, respectively. The reason for the higher incidence of thymomas observed in Chinese patients may be related to the presence of the Epstein-Barr virus genome in thymoma. Furthermore, all of the thymomas in our patients were lymphoepithelial and histologically resemble nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland. Both these tumours are closely linked to the Epstein-Barr virus and in Hong Kong, nasopharyngeal carcinoma is the third commonest cause of death from malignancy. We recommend early thymectomy for patients with myasthenia gravis particularly in geographical areas where there is a high incidence of nasopharyngeal carcinoma and undifferentiated carcinoma of the salivary gland.
Sujet(s)
Herpèsvirus humain de type 4 , Myasthénie/complications , Thymome/complications , Tumeurs du thymus/complications , Adolescent , Adulte , Sujet âgé , Enfant , Chine , Femelle , Humains , Mâle , Adulte d'âge moyen , Myasthénie/ethnologie , Myasthénie/microbiologie , Thymome/microbiologie , Tumeurs du thymus/microbiologieRÉSUMÉ
A systematic study of thymus homogenates and cell suspensions from 13 patients with myasthenia gravis (MG) of recent onset, and 6 non-myasthenic controls, has failed to detect or isolate virus by cell culture with 'rescue techniques', electron microscopy, or intracerebral inoculation into neonatal mice. These results do not support the case for persistent viral infection in the thymus, and impose constraints on hypotheses of a viral aetiology of MG.
Sujet(s)
Myasthénie/microbiologie , Thymus (glande)/microbiologie , Maladies virales/complications , Adolescent , Adulte , Animaux , Antigènes viraux/immunologie , Maladies auto-immunes/immunologie , Maladies auto-immunes/microbiologie , Lignée cellulaire , Enfant , Chlorocebus aethiops , Tests de fixation du complément , Femelle , Technique d'immunofluorescence , Humains , Mâle , Souris , Microscopie électronique , Myasthénie/étiologie , Papio , Lapins , Thymus (glande)/ultrastructureRÉSUMÉ
Thymic cells from 26 myasthenia gravis patients were investigated by viral isolation using inoculation of supernatants obtained from thymic tissue homogenates into human and monkey cells. Living cells from 14 thymuses were also cocultivated with monkey cell lines and with human embryonic lung fibroblasts. None of the thymic biopsies showed any cytopathic effect in these cell cultures sensitive to a broad spectrum of viruses. Cytomegalovirus antigen was not detected in any of 25 biopsies investigated in an imprint immunofluorescence assay.
Sujet(s)
Myasthénie/microbiologie , Thymus (glande)/microbiologie , Virus/isolement et purification , Antigènes viraux/analyse , Cytomegalovirus/immunologie , Femelle , Technique d'immunofluorescence , Humains , Mâle , Myasthénie/étiologie , Maladies virales/complicationsRÉSUMÉ
We investigated the hypothesis that a persistent viral infection of the thymus gland might trigger the autoimmune disease myasthenia gravis (MG). Thymus glands of nine patients with recent onset of MG were studied by a variety of techniques to detect the presence of occult viruses. No evidence of viral infection was found.
Sujet(s)
Myasthénie/microbiologie , Thymus (glande)/microbiologie , Adolescent , Adulte , Animaux , Maladies auto-immunes/microbiologie , Enfant , Virus à ADN , Femelle , Technique d'immunofluorescence , Humains , Mâle , Techniques microbiologiques , Adulte d'âge moyen , Muridae , Virus de la maladie de Newcastle , Techniques de culture d'organes , Poliovirus , Virus à ARN , Maladies virales/microbiologieRÉSUMÉ
The pathogenesis of myasthenia gravis is autoimmune, the real etiology, however, remains unknown. Virus has been suggested as an etiological agent of the disease. In this study we present 5 myasthenic patients, whose symptoms began a few weeks after a proven viral infection. The possibility of viral infection as etiology of myasthenia gravis is raised, and the mechanisms discussed.
Sujet(s)
Myasthénie/étiologie , Maladies virales/complications , Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Rougeole/complications , Myasthénie/microbiologieRÉSUMÉ
Virus has been suggested as an etiological agent in myasthenia gravis. In this investigation 36 patients with the clinical diagnosis of myasthenia gravis were tested for antibodies against ornithosis, mycoplasma pneumoniae and 16 viral antigens. Rabbits with experimentally induced autoimmune myasthenia gravis were similarly tested. There was no overall correlation to any microorganism, which might have suggested the involvement of a viral infection in the pathogenesis of the disease. Neither was there any difference in incidence of antibodies in female patients carrying the HLA B8 antigen, an antigen which is associated with myasthenia gravis, as compared to HLA B8 negative individuals.