RESUMEN
Patients with the autoimmune disease multiple sclerosis (MS) typically present with the clinically isolated syndromes (CIS) transverse myelitis (TM) or optic neuritis (ON). B-cell disturbances have been well documented in patients with MS and CIS patients with ON, but not in CIS patients with TM, despite the fact that these patients have the worst clinical outcome of all CIS types. The goal of this study was to characterize the B-cell populations and immunoglobulin genetics in TM patients. We found a unique expansion of CD27(high) plasmablasts in both the cerebrospinal fluid and periphery of TM patients that is not present in ON patients. Additionally, plasmablasts from TM patients show evidence for positive selection with increased somatic hypermutation accumulation in VH4(+) B cells and receptor editing that is not observed in ON patients. These characteristics unique to TM patients may impact disease severity and progression.
Asunto(s)
Linfocitos B/inmunología , Mielitis Transversa/inmunología , Células Plasmáticas/inmunología , Hipermutación Somática de Inmunoglobulina/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Adulto , Linfocitos B/citología , Linfocitos B/metabolismo , Proliferación Celular , Células Cultivadas , Citometría de Flujo , Reordenamiento Génico de Cadena Pesada de Linfocito B/genética , Reordenamiento Génico de Cadena Pesada de Linfocito B/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/inmunología , Región Variable de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/inmunología , Persona de Mediana Edad , Mielitis Transversa/sangre , Mielitis Transversa/líquido cefalorraquídeo , Células Plasmáticas/citología , Células Plasmáticas/metabolismo , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/metabolismo , Hipermutación Somática de Inmunoglobulina/genética , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Adulto JovenRESUMEN
B cells isolated from the CSF of patients with multiple sclerosis (MS) have a unique accumulation of somatic hypermutation within the B cell receptor, termed the antibody gene signature (AGS). The focus of this study was to investigate whether the AGS could also be detected in MS brain tissue. Genetic analysis of B cells isolated from post-mortem CNS tissue samples from four MS brains demonstrated that signature enriched B cells are present at the site of tissue injury as well as in the circulating CSF.
