Asunto(s)
Anticuerpos Monoclonales/metabolismo , Membrana Celular/metabolismo , Endocitosis/inmunología , Gangliósido G(M1)/metabolismo , Gangliósidos/metabolismo , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/genética , Factores de Ribosilacion-ADP/inmunología , Animales , Afinidad de Anticuerpos , Autoantígenos/inmunología , Autoantígenos/metabolismo , Transporte Biológico , Células CHO , Línea Celular Tumoral , Membrana Celular/inmunología , Cricetulus , Endosomas/inmunología , Endosomas/metabolismo , Gangliósido G(M1)/inmunología , Gangliósidos/inmunología , Expresión Génica , Humanos , Cinética , Ratones , Ratones Noqueados , Imagen Molecular , Neuronas/citología , Neuronas/inmunología , Neuronas/metabolismo , Unión Proteica , Imagen de Lapso de TiempoRESUMEN
Elevated titers of serum antibodies against GM1 ganglioside are associated with a variety of autoimmune neuropathies. Much evidence indicates these autoantibodies play a primary role in the disease processes, but the mechanism for their appearance is unclear. We studied the fine specificity of anti-GM1 antibodies of the IgG isotype present in sera from patients with Guillain-Barré syndrome (GBS), using thin-layer chromatogram-immunostaining of GM1, asialo-GM1 (GA1), GD1b and GM1-derivatives with small modifications on the oligosaccharide moiety. We were able to distinguish populations of antibodies with different fine specificity. Remarkably, individual patients presented only one or two of them, and different patients had different populations. This restriction in the variability of antibody populations suggests that the appearance of the anti-GM1 antibodies is a random process involving restricted populations of lymphocytes. With the origin of disease-associated anti-GM1 antibodies as a context, this finding could provide explanation for the "host susceptibility factor" observed in GBS following enteritis with GM1 oligosaccharide-carrying strains of Campylobacter jejuni.
Asunto(s)
Autoanticuerpos/inmunología , Gangliósido G(M1)/inmunología , Síndrome de Guillain-Barré/inmunología , Inmunoglobulina G/inmunología , Adolescente , Adulto , Anciano , Especificidad de Anticuerpos/inmunología , Autoanticuerpos/sangre , Autoinmunidad , Niño , Reacciones Cruzadas/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Clinical severity of Guillain-Barré syndrome (GBS) is highly variable, but the immunopathological reason is unknown. OBJECTIVE: The study was designed to show which antibody parameters are associated with disease severity in GBS patients with serum anti-GM1 IgG antibodies. METHODS: Thirty-four GBS patients with anti-GM(1) IgG antibodies were grouped into two categories according to disease severity at nadir: mild (grades 1-3 by Hughes functional scale, n=13) and severe (grades 4 and 5, n=21). Titre, affinity, fine specificity and cell binding of anti-GM(1) antibodies were obtained and compared between the two groups. RESULTS: No differences in antibody titre (GM(1)-ELISA) or affinity were found between the two patient groups. In contrast, the severe group showed a significantly higher frequency (95%, vs 46% in the mild group, p=0.002) of specific (not cross-reacting with GD(1b)) anti-GM(1) antibodies. In addition, the severe group also exhibited a higher antibody binding titre to cellular GM(1). CONCLUSIONS: Differences in fine specificity of antibodies are strong indications that different regions of the GM(1)-oligosaccharide are involved in antibody binding. High titres of specific anti-GM(1) antibody binding to cellular GM(1) can be explained by antigen exposure, that is, GM(1) exposes or forms mainly epitopes recognised by specific antibodies, and 'hides' those involved in binding of cross-reacting antibodies. Thus, the fine specificity of anti-GM(1) antibodies may influence disease severity by affecting antibody binding to cellular targets. Additionally, since antibody specificity studies are relatively easy to implement, fine specificity could be considered a useful predictor of disease severity.
Asunto(s)
Autoanticuerpos/inmunología , Gangliósido G(M1)/análogos & derivados , Gangliósido G(M1)/inmunología , Síndrome de Guillain-Barré/inmunología , Síndrome de Guillain-Barré/fisiopatología , Inmunoglobulina G/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Cromatografía en Capa Delgada , Evaluación de la Discapacidad , Ensayo de Inmunoadsorción Enzimática , Femenino , Gangliósidos/inmunología , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
High antibody affinity has been proposed as a disease determinant factor in neuropathies associated with anti-GM1 antibodies. An experimental model of Guillain-Barré syndrome, induced by immunization of rabbits with bovine brain gangliosides or GM1, was described recently (Yuki et al. [2001] Ann. Neurol. 49:712-720). We searched plasma from these rabbits, taken at disease onset and 1 or 2 weeks prior to onset, for the presence of high-affinity anti-GM1 IgG antibodies. Affinity was estimated by soluble antigen binding inhibition. High-affinity antibodies (binding inhibition by 10(-9) M GM1) were detected at disease onset but not before. No such difference was found for other antibody parameters such as titer, fine specificity, and population distribution. These findings support the proposed role of high affinity as an important factor in disease induction by anti-GM1 antibodies.