RESUMEN
Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients. All epitopes identified were located at loops connecting the ß strands of MOG. The most frequently recognized MOG epitope was revealed by the P42S mutation positioned in the CC'-loop. Overall, we distinguished seven epitope patterns, including the one mainly recognized by mouse mAbs. In half of the patients, the anti-MOG response was directed to a single epitope. The epitope specificity was not linked to certain disease entities. Longitudinal analysis of 11 patients for up to 5 y indicated constant epitope recognition without evidence for intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG still generated a long-lasting IgG response to vaccines, indicating that their loss of anti-MOG reactivity did not reflect a general lack of capacity for long-standing IgG responses. The majority of human anti-MOG Abs did not recognize rodent MOG, which has implications for animal studies. Our findings might assist in future detection of potential mimotopes and pave the way to Ag-specific depletion.
Asunto(s)
Enfermedades del Sistema Nervioso Central/inmunología , Epítopos/química , Epítopos/inmunología , Inflamación/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Adolescente , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Autoanticuerpos/inmunología , Autoanticuerpos/metabolismo , Enfermedades del Sistema Nervioso Central/genética , Niño , Preescolar , Epítopos/metabolismo , Femenino , Glicosilación , Humanos , Inmunoglobulina G/inmunología , Lactante , Inflamación/genética , Masculino , Ratones , Persona de Mediana Edad , Modelos Moleculares , Mutación , Glicoproteína Mielina-Oligodendrócito/genética , Glicoproteína Mielina-Oligodendrócito/metabolismo , Unión Proteica/inmunología , Conformación Proteica , Estabilidad Proteica , Alineación de Secuencia , Transfección , Adulto JovenRESUMEN
The performance of the 3M rapid detection influenza A+B (3M flu) assay was compared to the performance of other immunochromatographic assays. The clinical and analytical performance of the 3M flu assay was superior to that of BinaxNOW and Directigen EZ assays and equivalent to that of the QuickVue assay. The 3M flu assay offers an objective output and direct linkage to laboratory information systems.
Asunto(s)
Antígenos Virales/análisis , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/diagnóstico , Antígenos Virales/inmunología , Humanos , Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Sensibilidad y EspecificidadRESUMEN
We present histological, MRI, and clinical features of an adult patient with relapsing encephalomyelitis and antibodies against myelin oligodendrocyte glycoprotein (MOG). Furthermore, we report molecular details of the recognized epitope that is specific for human MOG. A brain biopsy revealed multiple sclerosis (MS)-type II pathology. Some features overlapped with both MS and neuromyelitis optica spectrum disorders (NMOSD), whereas others were distinct from both MS and NMOSD. Immunoadsorption and rituximab induced clinical stabilization. This case contributes a new, so far missing link in the emerging spectrum of MOG-antibody-associated encephalomyelitis.