ABSTRACT
El propósito de este estudio es el de comprobar el efecto in vivo de la terapia de anticuerpos anti-CD20 con Rituximab sobre los linfocitos T reguladores y la apoptosis de células inmunitarias en pacientes con artritis reumatoidea (RA). En un ensayo piloto abierto, se administró Rituximab (1,0 g en los días 1 y 30) a siete pacientes con RA que eran refractarios a la terapia convencional. Se obtuvieron muestras de sangre periférica en los días 0, 15 y 180 de terapia con Rituximab, analizándose el número y funcionalidad de linfocitos T reguladores, así como la presencia de células apoptóticas. Cinco de los siete pacientes mostraron una mejora clínica significativa tras el tratamiento por Rituximab (respuesta ACR 50-70), y también un aumento del número y la función de las células T reguladoras. Además, se detectó un incremento en el porcentaje de células apoptóticas en sangre periférica al inicio de la terapia con Rituximab. Estos datos sugieren que Rituximab ejerce un efecto de interés sobre las células T reguladoras en pacientes con RA, un fenómeno que puede contribuir al efecto terapéutico de este anticuerpo anti-CD20 en RA
The aim of this study was to assess the in vivo effect of anti- CD20 therapy with Rituximab on regulatory T lymphocytes, and apoptosis of immune cells in patients with rheumatoid arthritis (RA). In an open and pilot clinical trial, Rituximab was administered (1.0 g at days 1 and 30) to seven patients with RA that were refractory to conventional therapy. Peripheral blood samples were obtained at days 0, 15, and 180 of Rituximab therapy, and the number and function of regulatory T lymphocytes, as well as the presence of apoptotic cells were analyzed. Five out of seven patients showed significant clinical improvement upon Rituximab therapy (ACR response 50-70), and a significant increase in the number and function of regulatory T cells. In addition, an increased percent of apoptotic cells was detected in the peripheral blood after the onset of Rituximab therapy. These data suggest that Rituximab seems to exert an interesting effect on regulatory T cells in patients with RA; this phenomenon may contribute to the therapeutic effect of this anti-CD20 agent in RA
Subject(s)
Female , Humans , Antigens, CD20/immunology , Arthritis, Rheumatoid/drug therapy , T-Lymphocytes/immunology , Apoptosis/immunology , Arthritis, Rheumatoid/immunology , T-Lymphocytes , ApoptosisABSTRACT
The aim of this study was to assess the effect of Adalimumab on different immune parameters in patients with RA. Adalimumab was administered (40 mg every other week for 26 weeks) to eight patients with RA that were refractory to conventional drug therapy. Peripheral blood samples were obtained at days 0, 15 and 180 of Adalimumab therapy, and the following immune parameters were assessed: Number, phenotype, and function of regulatory T lymphocytes. The induction of apoptosis of immune cells and the in vitro and in vivo reactivity towards M. tuberculosis were also analysed. All patients responded to Adalimumab (ACR response 50-70), and a modest but significant increase in the number and function of regulatory T cells was observed at day 15 of anti-TNF-alpha therapy. In addition, an increased percent of apoptotic cells was detected in the peripheral blood at day 15 of Adalimumab therapy. Unexpectedly, most of these effects were not further observed at day 180. However, two patients showed a persistent and marked reduction in the reactivity to M. tuberculosis. Although we have found that Adalimumab affects the number and function of regulatory T lymphocytes, and the apoptosis of immune cells, these effects are transient and its possible causal relationship with the therapeutic activity of this biological agent remains to be determined. Nevertheless, the down-regulatory effect of Adalimumab on the reactivity to M. tuberculosis could be related to an enhanced risk of tuberculosis reactivation.
