RESUMEN
Neuromyelitis optica (NMO) predominantly affects women, some in childbearing age, and requires early therapeutic intervention to prevent disabling relapses. We report an anti-AQP4 antibody-seropositive patient who became pregnant seven months after low-dose (100 mg) rituximab application. Pregnancy showed no complications, and low-dose rituximab restarted two days after delivery resulted in neurological stability for 24 months. Remarkably, her otherwise healthy newborn presented with anti-AQP4 antibody and reduced B lymphocyte counts in umbilical cord blood, which normalized three months later. Confirming and extending previous reports, our case suggests that low-dose rituximab might be compatible with pregnancy and prevent rebound NMO disease activity postpartum.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Acuaporina 4/inmunología , Autoanticuerpos/sangre , Linfocitos B/inmunología , Factores Inmunológicos/uso terapéutico , Recién Nacido/sangre , Neuromielitis Óptica/inmunología , Complicaciones del Embarazo/inmunología , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Autoantígenos/inmunología , Femenino , Sangre Fetal/inmunología , Humanos , Factores Inmunológicos/administración & dosificación , Recién Nacido/inmunología , Depleción Linfocítica , Neuromielitis Óptica/sangre , Neuromielitis Óptica/tratamiento farmacológico , Periodo Posparto , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/tratamiento farmacológico , Rituximab , Prevención Secundaria , Adulto JovenRESUMEN
OBJECTIVE: To study the longitudinal dynamics of anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases. METHODS: We addressed the kinetics of anti-MOG immunoglobulins in a prospective study comprising 77 pediatric patients. This was supplemented by a cross-sectional study analyzing 126 pediatric patients with acute demyelination and 62 adult patients with multiple sclerosis (MS). MOG-transfected cells were used for detection of antibodies by flow cytometry. RESULTS: Twenty-five children who were anti-MOG immunoglobulin (Ig) positive at disease onset were followed for up to 5 years. Anti-MOG antibodies rapidly and continuously declined in all 16 monophasic patients with acute disseminated encephalomyelitis and in one patient with clinically isolated syndrome. In contrast, in 6 of 8 patients (75%) eventually diagnosed with childhood MS, the antibodies to MOG persisted with fluctuations showing a second increase during an observation period of up to 5 years. Antibodies to MOG were mainly IgG 1 and their binding was largely blocked by pathogenic anti-MOG antibodies derived from a spontaneous animal model of autoimmune encephalitis. The cross-sectional part of our study elaborated that anti-MOG Ig was present in about 25% of children with acute demyelination, but in none of the pediatric or adult controls. Sera from 4/62 (6%) adult patients with MS had anti-MOG IgG at low levels. CONCLUSIONS: The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination.
Asunto(s)
Autoanticuerpos/análisis , Encefalomielitis Aguda Diseminada/inmunología , Glicoproteína Asociada a Mielina/inmunología , Adolescente , Adulto , Unión Competitiva , Línea Celular , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Inmunoglobulina G/análisis , Inmunoglobulinas/análisis , Lactante , Cinética , Estudios Longitudinales , Masculino , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Proteínas de la Mielina , Glicoproteína Mielina-Oligodendrócito , Estudios Prospectivos , TransfecciónRESUMEN
BACKGROUND: Neuromyelitis optica (NMO) is a severe autoimmune disease targeting optic nerves and spinal cord. The monoclonal anti-CD20 B-cell antibody rituximab is an emerging therapeutic option in NMO. However, neither long-term efficacy or safety of rituximab, nor the correlation between B-cell counts, B-cell fostering cytokines, aquaporin-4 antibodies (AQP4-ab), and disease activity in NMO, have been investigated prospectively. METHODS: We performed a prospective long-term cohort study of 10 patients with NMO who were treated up to 5 times with rituximab as a second-line therapy. Clinical examinations, B-cell counts, and serum concentrations of BAFF (B-cell activating factor of the TNF family; also called TNFSF13b), APRIL (a proliferation-inducing ligand; also called TNFSF13), AQP4-ab, and immunoglobulin levels were measured every 3 months. RESULTS: Repeated treatment with rituximab led to sustained clinical stabilization in most patients with NMO. Disease activity correlated with B-cell depletion, but not clearly with AQP4-ab or levels of APRIL. BAFF levels increased after application of rituximab and indicated persisting efficacy of the drug but did not correlate with disease activity. Overall, rituximab was well-tolerated even after up to 5 consecutive treatment courses; however, we observed several severe adverse reactions. CONCLUSION: Our data indicate that long-term therapy with rituximab is effective in NMO as a second-line therapy and has an acceptable safety profile. Retreatment with rituximab should be applied before reappearance of circulating B cells. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Factores Inmunológicos/administración & dosificación , Neuromielitis Óptica/tratamiento farmacológico , Adolescente , Adulto , Anticuerpos/sangre , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Acuaporina 4/inmunología , Factor Activador de Células B/sangre , Linfocitos B , Estudios de Cohortes , Esquema de Medicación , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Recuento de Leucocitos , Estudios Longitudinales , Masculino , Neuromielitis Óptica/fisiopatología , Concentración Osmolar , Estudios Prospectivos , Rituximab , Resultado del Tratamiento , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/sangreRESUMEN
In neuromyelitis optica (NMO), the monoclonal B-cell antibody rituximab is a therapeutic option. Little is known about the course of NMO and the safety of rituximab during pregnancy. In this study, we report the clinical course of a patient with NMO after application of rituximab 1 week before inadvertent conception. Mother and child did not experience any adverse event, and the postpartum development of the baby was completely normal up to 15 months. Clinical course of NMO was stable during the entire pregnancy. This case illustrates a favorable outcome in a pregnant NMO patient and her child after therapy with rituximab.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Factores Inmunológicos/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Embarazo no Planeado , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Lactante , Recién Nacido , Nacimiento Vivo , Embarazo , Recurrencia , Rituximab , Resultado del Tratamiento , Adulto JovenAsunto(s)
Anticuerpos/sangre , Proteínas de Unión al GTP/genética , Interferón beta/efectos adversos , Interferón beta/inmunología , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Adulto , Anticuerpos/efectos de los fármacos , Biomarcadores/sangre , Femenino , Humanos , Masculino , Esclerosis Múltiple/sangre , Proteínas de Resistencia a Mixovirus , Valor Predictivo de las Pruebas , Factores de Tiempo , Activación Transcripcional/efectos de los fármacos , Activación Transcripcional/inmunología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunologíaRESUMEN
BACKGROUND: Parkinson disease (PD) is often difficult to distinguish from parkinsonian syndromes of other causes in early stages of the disease. In search of a suitable endocrinologic challenge test, we investigated dopaminergic sensitivity in patients with de novo parkinsonian syndromes. OBJECTIVE: We measured the growth hormone (GH) response to a subthreshold dose of the dopamine 1-dopamine 2 receptor agonist apomorphine hydrochloride to differentiate parkinsonian syndromes from PD. PATIENTS AND METHODS: Seventeen patients with a clinical diagnosis of PD, 16 patients with a clinical diagnosis of multiple system atrophy, and 11 healthy controls. The GH response to a subthreshold dosage of apomorphine and to somatorelin (GH-releasing factor) was tested in a randomized order; on the third day the protocol was repeated with a clinically effective dose of apomorphine. RESULTS: The GH response to the low dose of apomorphine was significantly increased in patients with PD when compared with patients with multiple system atrophy or the control subjects (multivariate analyses of covariance; univariate F test, all P<.05). In contrast, there were no significant group differences with use of the higher dose of apomorphine or in the somatorelin-induced GH release. CONCLUSIONS: The GH response to a subthreshold dose of apomorphine appears to be a useful tool to identify patients with PD vs multiple system atrophy. The enhanced GH response to a subthreshold dopaminergic stimulus may reflect a hypersensitivity of the extrastriatal dopamine receptors in PD.