RESUMEN
BACKGROUND: Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma. OBJECTIVE: In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated. METHODS: Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1. RESULTS: Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells. CONCLUSIONS: Taken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma.
Asunto(s)
Asma/inmunología , Subgrupos de Linfocitos B/inmunología , Adulto , Asma/fisiopatología , Subgrupos de Linfocitos B/metabolismo , Antígeno CD24/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Inmunofenotipificación , Interleucina-10/metabolismo , Lipopolisacáridos/inmunología , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Fenotipo , Pruebas de Función Respiratoria , Factores de Riesgo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptor Toll-Like 4/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Adulto JovenRESUMEN
The authors describe the case of a 22-year-old woman with involuntary contractions of the sternocleidomastoid and trapezius muscles that resulted in turning movements of the head. The jerks displayed the clinical and neurophysiological characteristics of segmental myoclonus (SM) restricted to muscles supplied bilaterally by the first four cervical segments. Magnetic resonance imaging disclosed a tumor in the midline above the cisterna magna that was later histologically proven to be a choroid plexus papilloma. The patient's involuntary movements did not extend to other muscle groups or, in particular, to the palate, as one might have expected in the case of brainstem lesions. Myoclonus was the sole clinical manifestation of the tumor in this patient; other signs and symptoms invariably reported in other cases of posterior fossa papilloma, such as increased intracranial pressure or cranial nerve palsies, were absent. Release from suprasegmental control is suggested as a possible pathophysiological mechanism in this case of SM.