Sujet(s)
Anticorps monoclonaux d'origine murine/usage thérapeutique , Autoanticorps/sang , Protéines membranaires/immunologie , Protéines de tissu nerveux/immunologie , Syndromes paranéoplasiques/traitement médicamenteux , Syndromes paranéoplasiques/immunologie , Résistance aux substances , Humains , Facteurs immunologiques/usage thérapeutique , Adulte d'âge moyen , Syndromes paranéoplasiques/sang , Syndromes paranéoplasiques/diagnostic , RituximabSujet(s)
Adénocarcinome/complications , Antigènes néoplasiques/immunologie , Encéphalite limbique/étiologie , Protéines de tissu nerveux/immunologie , Troubles de la motilité oculaire/étiologie , Tumeurs de l'estomac/complications , Adénocarcinome/anatomopathologie , Autoanticorps/immunologie , Encéphale/anatomopathologie , Humains , Imagerie par résonance magnétique , Mâle , Adulte d'âge moyen , Tumeurs de l'estomac/anatomopathologieSujet(s)
Encéphalite à anticorps anti-récepteur N-méthyl-D-aspartate/anatomopathologie , Encéphale/anatomopathologie , Encéphalomyélite aigüe disséminée/anatomopathologie , Neurofibres non-myélinisées/anatomopathologie , Adulte , Encéphalite à anticorps anti-récepteur N-méthyl-D-aspartate/immunologie , Autoanticorps/immunologie , Diagnostic différentiel , Femelle , Humains , Imagerie par résonance magnétiqueRÉSUMÉ
BACKGROUND AND PURPOSE: Anti-N-methyl-D-asparate (NMDA) receptor encephalitis is thought to be antibody-mediated. To perform an immunohistopathological study of the inflammatory reaction in a brain biopsy performed before immunomodulatory treatments in a patient with anti-NMDA receptor encephalitis. METHODS: An immunohistochemical study was performed using CD3, CD68, CD20, CD138 and CD1a antibodies. RESULTS: Prominent B-cell cuffing was present around brain vessels accompanied by some plasma cells, while macrophages and T cells were scattered throughout the brain parenchyma. CONCLUSION: These findings suggest that the B cells interact with the T cells and are involved in antibody secretion by the plasma cells.
Sujet(s)
Maladies auto-immunes du système nerveux/immunologie , Maladies auto-immunes du système nerveux/anatomopathologie , Encéphalite/immunologie , Encéphalite/anatomopathologie , Récepteurs du N-méthyl-D-aspartate/immunologie , Adolescent , Autoanticorps/effets indésirables , Autoanticorps/sang , Lymphocytes B/immunologie , Lymphocytes B/anatomopathologie , Artères cérébrales/immunologie , Artères cérébrales/anatomopathologie , Femelle , Humains , Lymphocytes T/immunologie , Lymphocytes T/anatomopathologie , Vascularite du système nerveux central/immunologie , Vascularite du système nerveux central/anatomopathologieRÉSUMÉ
OBJECTIVE: Anti-Hu antibodies (Hu-Ab) and anti-CV2/CRMP5 antibodies (CV2/CRMP5-Ab) have been identified in association with paraneoplastic neurological disorders. However, it is not clear whether these antibodies are associated with specific neurological symptoms or are only markers of anti-cancer immune reaction. METHODS: To address this question, 37 patients with CV2/CRMP5-Ab and 324 patients with Hu-Ab were compared. RESULTS: Whereas the age and sex ratio were the same between the two groups, the distribution of neurological symptoms was not. Patients with CV2/CRMP5-Ab presented more frequently cerebellar ataxia, chorea, uveo/retinal symptoms and myasthenic syndrome (Lambert-Eaton myasthenic syndrome LEMS or myasthenia gravis). They also had a better Rankin score. In contrast, dysautonomia, brainstem encephalitis and peripheral neuropathy were more frequent in patients with Hu-Ab. Limbic encephalitis occurred similarly in both groups. Small-cell lung cancer was the most frequently associated tumour in both groups of patients, while malignant thymoma was observed only in patients with CV2/CRMP5-Ab. In particular, patients with CV2/CRMP5-Ab and thymoma developed myasthenic syndrome more frequently, while patients with SCLC developed neuropathies more frequently. Chorea and myasthenic syndrome were only seen in patients with CV2/CRMP5-Ab. The median survival time was significantly longer in patients with CV2/CRMP5-Ab, and this effect was not dependent on the type of tumour. INTERPRETATION: The data demonstrate that in patients with paraneoplastic neurological syndromes, the neurological symptoms and survival vary with both the type of associated onco-neural antibody and the type of tumour.
Sujet(s)
Tumeurs du cerveau/immunologie , Tumeurs du cerveau/anatomopathologie , Antigènes Hu de l'encéphalomyélite paranéoplasique/immunologie , Protéines de tissu nerveux/immunologie , Syndromes neurologiques paranéoplasiques/immunologie , Syndromes neurologiques paranéoplasiques/anatomopathologie , Adulte , Âge de début , Sujet âgé , Anticorps antitumoraux/immunologie , Tumeurs du cerveau/épidémiologie , Femelle , Humains , Hydrolases , Mâle , Protéines associées aux microtubules , Adulte d'âge moyen , Maladies du système nerveux/étiologie , Maladies du système nerveux/physiopathologie , Syndromes neurologiques paranéoplasiques/épidémiologie , Pronostic , Analyse de survie , Thymome/anatomopathologieRÉSUMÉ
The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of four homologous phosphoproteins considered crucial for brain development. Autoantibodies produced against member(s) of this family by patients with paraneoplastic neurological diseases have made it possible to clone a fifth human Ulip/CRMP and characterize its cellular and anatomical distribution in developing brain. This protein, referred to as Ulip6/CRMP5, is highly expressed during rat brain development in postmitotic neural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precursors at certain times during development and in oligodendrocytes in the adult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A) signal in developing neurons, in studies to understand the function of Ulip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendrocytes were cultured in a Sema3A-conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major Sema3A receptor component. In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pathway that modulates oligodendrocyte process extension mediated by neuropilin-1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigation of neuron/oligodendrocyte interactions in the normal and pathological brain.
Sujet(s)
Glycoprotéines , Glycoprotéines/métabolisme , Protéines de tissu nerveux/biosynthèse , Protéines de tissu nerveux/métabolisme , Oligodendroglie/métabolisme , Animaux , Anticorps/pharmacologie , Encéphale/embryologie , Encéphale/croissance et développement , Encéphale/métabolisme , Cellules cultivées , Facteurs de croissance endothéliale/pharmacologie , Femelle , Glycoprotéines/pharmacologie , Humains , Hydrolases , Immunohistochimie , Hybridation in situ , Protéines et peptides de signalisation intercellulaire , Lymphokines/pharmacologie , Mâle , Souris , Protéines associées aux microtubules , Données de séquences moléculaires , Protéines de tissu nerveux/antagonistes et inhibiteurs , Protéines de tissu nerveux/génétique , Protéines de tissu nerveux/isolement et purification , Neurites/effets des médicaments et des substances chimiques , Neurites/métabolisme , Neuropiline 1 , Oligodendroglie/cytologie , Oligodendroglie/effets des médicaments et des substances chimiques , Spécificité d'organe , Phosphoprotéines/biosynthèse , Phosphoprotéines/génétique , Phosphoprotéines/isolement et purification , ARN messager/biosynthèse , ARN messager/génétique , Rats , Sémaphorine-3A , Similitude de séquences d'acides aminés , Transduction du signal/effets des médicaments et des substances chimiques , Transduction du signal/physiologie , Facteur de croissance endothéliale vasculaire de type A , Facteurs de croissance endothéliale vasculaireSujet(s)
Autoanticorps/immunologie , Autoantigènes/immunologie , Maladies auto-immunes du système nerveux/immunologie , Métastases d'origine inconnue/diagnostic , Syndromes neurologiques paranéoplasiques/immunologie , Adulte , Sujet âgé , Animaux , Spécificité des anticorps , Maladies auto-immunes du système nerveux/étiologie , Tumeurs du sein/complications , Tumeurs du sein/immunologie , Carcinome canalaire du sein/complications , Carcinome canalaire du sein/immunologie , Carcinome à petites cellules/complications , Carcinome à petites cellules/immunologie , Femelle , Humains , Tumeurs du poumon/complications , Tumeurs du poumon/immunologie , Métastase lymphatique/immunologie , Mâle , Adulte d'âge moyen , Métastases d'origine inconnue/immunologie , Oligodendroglie/immunologie , Dégénérescence cérébelleuse paranéoplasique/étiologie , Dégénérescence cérébelleuse paranéoplasique/immunologie , Neuropathie paranéoplasique/étiologie , Neuropathie paranéoplasique/immunologie , Syndromes neurologiques paranéoplasiques/étiologie , Polyradiculoneuropathie/étiologie , Polyradiculoneuropathie/immunologie , Cellules de Purkinje/immunologie , Rats , Thymome/complications , Thymome/immunologie , Tumeurs du thymus/complications , Tumeurs du thymus/immunologie , Uvéite/immunologieRÉSUMÉ
The family of collapsin response mediator protein/Unc-33-like protein (CRMP/Ulip), composed of four homologous members, is specifically and highly expressed in the nervous system during embryonic neuronal development and dramatically down-regulated in the adult. Members of this family have been proposed to be part of the semaphorins signal transduction pathway involved in axonal outgrowth. Here, we show by in situ hybridization and immunohistochemistry that CRMP2/Ulip2, and to a lesser extent CRMP3/Ulip4, are expressed in immature and mature oligodendrocytes, but not in astrocytes. Transcripts encoding the other CRMP/Ulip members are also detectable by RT-PCR in highly purified mature oligodendrocytes. Interestingly, in the adult, the protein CRMP2/Ulip2 is mainly detectable in subsets of oligodendrocytes distributed according to an increasing rostrocaudal gradient, with the largest number of positive cells being present in the brain stem and spinal cord. In cultures of highly purified oligodendrocytes, however, CRMP2/Ulip2 was detectable in all the cells. Addition of Sema3A in the culture medium completely inhibited the emergence of oligodendrocyte processes suggesting that, as in neurons, a Sema3A signaling pathway mediated via CRMP2/Ulip2 may be involved in the regulation of oligodendroglial process outgrowth.
Sujet(s)
Corps calleux/cytologie , Protéines de tissu nerveux/génétique , Oligodendroglie/physiologie , Animaux , Séparation cellulaire , Corps calleux/croissance et développement , Régulation de l'expression des gènes au cours du développement , Glycoprotéines/pharmacologie , Cellules HeLa , Humains , Immunohistochimie , Hybridation in situ , Protéines et peptides de signalisation intercellulaire , Opéron lac , Mâle , Souris , Souris transgéniques , Protéines de tissu nerveux/analyse , Oligodendroglie/composition chimique , Oligodendroglie/cytologie , Nerf optique/cytologie , Nerf optique/croissance et développement , ARN messager/analyse , Rats , Rat Sprague-Dawley , RT-PCR , Sémaphorine-3A , Transduction du signal/effets des médicaments et des substances chimiques , Transduction du signal/physiologie , Moelle spinale/cytologie , Moelle spinale/croissance et développementRÉSUMÉ
Anti-CV2 autoantibodies have recently been discovered in patients with paraneoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti-CV2 autoantibodies recognize a brain protein of 66 kDa developmentally regulated and specifically expressed by a subpopulation of oligodendrocytes in the adult brain. Here, we demonstrate that anti-CV2 sera recognize several post-translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous to the Unc-33 gene product in Caenorhabditis elegans. The sequence of the human Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2-q26, a region mutated in glioblastomas and containing tumour suppressor genes. The identification of the Ulip/CRMP proteins as recognized by anti-CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendrocytes and into pathophysiology of PND.
Sujet(s)
Autoanticorps/métabolisme , Protéines du muscle , Protéines de tissu nerveux/immunologie , Syndromes neurologiques paranéoplasiques/immunologie , Phosphoprotéines/immunologie , Séquence d'acides aminés , Animaux , Spécificité des anticorps/immunologie , Séquence nucléotidique , Cartographie chromosomique , Chromosomes humains de la paire 10/génétique , ADN complémentaire/génétique , Épitopes/génétique , Épitopes/immunologie , Cellules HeLa , Humains , Immunotransfert , Hybridation in situ , Souris , Données de séquences moléculaires , Protéines de tissu nerveux/génétique , Maturation post-traductionnelle des protéines/immunologie , Similitude de séquences d'acides aminés , TransfectionRÉSUMÉ
INTRODUCTION: Paraneoplastic neurological syndromes (PNS) refer to a set of neurological disorders associated with neuronal degeneration in some patients with systemic cancers. These disorders are not related to the tumor mass or metastasis. CURRENT KNOWLEDGE AND KEY POINTS: Evidence argues for an autoimmune reaction against tumor cells which expresses antigens normally present in neurons. A high percentage of patients with PNS harbors high titers of anti-neuronal autoantibodies in their serum and cerebrospinal fluid. In addition to their clinical interest in diagnosis and pathophysiology, these autoantibodies provide a unique opportunity to identify genes encoding previously undiscovered neuronal proteins which are also expressed by tumor cells. These "onconeural" antigens have been classified in four groups: neuromuscular junction proteins, nerve terminal/vesicle-associated proteins, neuronal RNA binding proteins, or neuronal signal transduction proteins. FUTURE PROSPECTS AND PROJECTS: All of these proteins would play a major role in the neuronal maturation and homeostasis, and for some of them in cellular proliferation. Better understanding of the exact role of these proteins would in turn permit better understanding of the mechanisms of neuronal degeneration and tumor cell proliferation in PNS.
Sujet(s)
Maladies du système nerveux/physiopathologie , Neurones/immunologie , Syndromes paranéoplasiques/physiopathologie , Autoanticorps/sang , Maladies auto-immunes/physiopathologie , Humains , Maladies du système nerveux/immunologie , Syndromes paranéoplasiques/diagnostic , Syndromes paranéoplasiques/immunologieRÉSUMÉ
Nucleocapsid protein (NCp7) of human immunodeficiency virus type 1 is found covering the genomic RNA in the interior of the viral particle. It is a highly basic protein with two zinc fingers of the form CX2CX4HX4C which exhibit strong affinity for a zinc cation. To study the structure-function relationship of the N-terminal zinc finger of NCp7, this domain was either deleted or changed to CX2CX4CX4C. We examined virus formation and structure as well as proviral DNA synthesis. Our data show that these two NC mutations result in the formation of particles with an abnormal core morphology and impair the end of proviral DNA synthesis, leading to noninfectious viruses.
Sujet(s)
Protéines de capside , Capside/physiologie , Produits du gène gag/physiologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/physiologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/ultrastructure , Protéines virales , Réplication virale , Doigts de zinc/physiologie , Capside/génétique , ADN viral , Produits du gène gag/génétique , Produits du gène gag/métabolisme , Cellules HeLa , Humains , Mutagenèse , Relation structure-activité , Cellules cancéreuses en culture , Virion/ultrastructure , Produits du gène gag du virus de l'immunodéficience humaineRÉSUMÉ
HIV genomic RNA resides within the nucleocapsid, in the interior of the virus, which serves to protect the RNA against nuclease degradation and to promote its reverse transcription. To investigate the role of nucleocapsid protein (NCp7) in the stability and replication of genomic RNA within the nucleocapsid, we used NCp7, reverse transcriptase (RT) and RNAs representing the 5' and 3' regions of the genome to reconstitute functional HIV-1 nucleocapsids. The nucleoprotein complexes generated in vitro were found to be stable, which, according to biochemical and genetic data, probably results from the tight binding of NCp7 molecules to the RNA and strong NCp7/NCp7 interactions. The nucleoprotein complexes efficiently protected viral RNA against RNase degradation and, at the same time, promoted viral DNA synthesis by RT. DNA strand transfer from the 5' to the 3' RNA template was very efficient in nucleoprotein complexes formed in the presence of both RNAs, but not when the RNAs were in separate complexes. These results indicate that the in vitro reconstituted HIV-1 nucleoprotein complexes function like virion nucleocapsids and thus provide a way to study at the molecular level this viral substructure and the synthesis of proviral DNA, and to search for new anti-HIV agents.
Sujet(s)
Protéines de capside , Capside/métabolisme , ADN viral/biosynthèse , Produits du gène gag/métabolisme , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/métabolisme , ARN viral/métabolisme , Protéines virales , Séquence nucléotidique , Capside/génétique , Amorces ADN , ADN complémentaire/biosynthèse , ADN simple brin/biosynthèse , Électrophorèse sur gel de polyacrylamide , Produits du gène gag/génétique , Transcriptase inverse du VIH , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Humains , Données de séquences moléculaires , Réaction de polymérisation en chaîne , ARN viral/génétique , RNA-directed DNA polymerase/métabolisme , Protéines de fusion recombinantes/génétique , Ribonuclease T1/métabolisme , Matrices (génétique) , Doigts de zinc , Produits du gène gag du virus de l'immunodéficience humaineRÉSUMÉ
A sandwich enzyme-linked immunosorbent assay to detect staphylococcal enterotoxin B was developed using rat monoclonal antibodies as capture antibodies and as a biotinylated conjugate. This test was sensitive, less than 1 ng/ml of enterotoxin B was detected and interference by protein A was prevented by the use of rat monoclonal antibodies of the IgG2a isotype which were insensitive to protein A even at concentrations greater than 1000 ng/ml.
Sujet(s)
Anticorps monoclonaux , Entérotoxines/analyse , Test ELISA , Protéine A staphylococcique , Staphylococcus aureus , Animaux , Anticorps monoclonaux/immunologie , Biotine , Réactions croisées , Femelle , Immunoglobuline G/immunologie , Valeur prédictive des tests , RatsRÉSUMÉ
Lectinlike adhesins were identified in the Bacteroides fragilis group by using sugars immobilized on agarose beads either with whole bacteria by direct microscopic examination or with soluble extracts by immunoaffinoelectrophoresis. These two methods allowed the identification of two sugars reacting with whole bacteria and with the corresponding extracts: alpha-D-glucosamine and D-galactosamine. Among eight strains tested representing seven species, the two strains of B. fragilis were equally adhesive and showed the greatest adhesions. The lectinlike adhesin was purified by affinity chromatography on glucosamine-agarose or galactosamine-agarose and showed one band at 70,000 daltons in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This lectinlike adhesin may help to elucidate the roles of the B. fragilis group in the colonization of intestinal surfaces and in the predominance of B. fragilis in infections alone and in synergy with other bacteria.