Evaluación histológica e inmunohistoquímica secuencial de marcadores de proliferación y apoptosis durante el tratamiento de la psoriasis con anti-factor de necrosis tumoral; (infliximab) / Sequential Histological and ImmunohistochemicalAssessment of Proliferation and ApoptoticMarkers During Treatment of Psoriasiswith Antitumor Necrosis Factor α (Infliximab)

Introducción y objetivos. La psoriasis es una enfermedad inflamatoria cutánea de naturaleza inmunológica mediada por citoquinas de tipo Th1. El tratamiento con anticuerpos anti-factor de necrosis tumoral α (TNF-α) (infliximab) ha proporcionado respuestas clínicas significativas; sin embargo, los mecanismos implicadosen la curación no están bien aclarados. El objetivo del presente trabajo es evaluar las variaciones de la histología y en la expresión de marcadores de proliferación y apoptosis, en biopsias cutáneas secuenciales de pacientes con psoriasis tratados con in fliximab. Material y métodos. Se estudiaron biopsias de piel (sana y lesionada) de 3 pacientes afectados de psoriasis generalizada moderada-grave (índice de área y gravedad de la soriasis [PASI]: 35 de media) tratados con infusiones por vía intravenosa de infliximab (5 mg/kg) en las semanas 0, 2 y 6. Las biopsias se realizaron en los días 0, 14 y 28, y fueron procesadas para estudio histológico convencional e inmunohistoquímico con marcadores de apoptosis–TP53, BCL-2 y anticaspasas 3 y 8– y de proliferación celular –Ki67–. Resultados. El tratamiento con infliximab se asoció con una significativa mejoría clínica en los 3 pacientes (PASI medio: 21,6 a los 14 días y 13,9 a las 6 semanas), que se correlacionó con la desaparición progresiva de las lesiones histológicas, con disminución de la proliferación epidérmica. Sin embargo, no observamos imágenes de apoptosis ni obtuvimos positividad con los anticuerpos anticaspasas. La expresión de TP53 disminuyó a las2 semanas del inicio del tratamiento, siendo similar a la piel normal a los 28 días. Conclusiones. La respuesta clínica e histológica de la psoriasis con infliximab no se asoció a un incremento significativo en los marcadores de apoptosis evaluados (AU)

Background and objectives. Psoriasis is an inflammatory skin disease of immunologic nature that is mediated by T-helper-1 cytokines. Clinical response to treatment with antitumor necrosis factor (TNF) –α antibodies (infliximab) has been significant; however, the mechanisms for clearance of lesions have not been elucidated. The aim of the present study was to assess variations in the histology and expression of proliferation and apoptotic markers in sequential skin biopsies of patients with psoriasis treated with infliximab. Material and methods. We studied skin biopsies (of lesioned and healthy skin) from 3 patients with extensive moderate-to-severe psoriasis (mean psoriasis area and severity index [PASI] score, 35) treated with intravenous infliximab infusions (5 mg/kg) at weeks 0, 2, and 6. Biopsies were taken on days 0, 14, and 28, and were processed for conventional histological and immunohistochemical study. The apoptotic markers used were TP53, B-cell lymphoma 2 protein, anticaspase 3, and anticaspase 8. The cell proliferation marker used was Ki67. Results. Treatment with infliximab was associated with a significant clinical improvement in 3 patients (mean PASI score, 21.6 at 14 days and 13.9 at 6 weeks), which correlated with the progressive disappearance of histological lesions with a decrease in epidermal proliferation. However, apoptosis was not observed, and the samples tested negative for anticaspase antibodies. Expression of TP53 decreased 2 weeks after starting treatment, and was similar to that in normal skin at 28 days. Conclusions. Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed (AU)

[Sequential histological and immunohistochemical assessment of proliferation and apoptotic markers during treatment of psoriasis with antitumor necrosis factor alpha (infliximab)]. / Evaluación histológica e inmunohistoquímica secuencial de marcadores de proliferación y apoptosis durante el tratamiento de la psoriasis con anti-factor de necrosis tumoral alpha (infliximab).

BACKGROUND AND OBJECTIVES: Psoriasis is an inflammatory skin disease of immunologic nature that is mediated by T-helper-1 cytokines. Clinical response to treatment with antitumor necrosis factor (TNF) alpha antibodies (infliximab) has been significant; however, the mechanisms for clearance of lesions have not been elucidated. The aim of the present study was to assess variations in the histology and expression of proliferation and apoptotic markers in sequential skin biopsies of patients with psoriasis treated with infliximab. MATERIAL AND METHODS: We studied skin biopsies (of lesioned and healthy skin) from 3 patients with extensive moderate-to-severe psoriasis (mean psoriasis area and severity index [PASI] score, 35) treated with intravenous infliximab infusions (5 mg/kg) at weeks 0, 2, and 6. Biopsies were taken on days 0, 14, and 28, and were processed for conventional histological and immunohistochemical study. The apoptotic markers used were TP53, B-cell lymphoma 2 protein, anticaspase 3, and anticaspase 8. The cell proliferation marker used was Ki67. RESULTS: Treatment with infliximab was associated with a significant clinical improvement in 3 patients (mean PASI score, 21.6 at 14 days and 13.9 at 6 weeks), which correlated with the progressive disappearance of histological lesions with a decrease in epidermal proliferation. However, apoptosis was not observed, and the samples tested negative for anticaspase antibodies. Expression of TP53 decreased 2 weeks after starting treatment, and was similar to that in normal skin at 28 days. CONCLUSIONS: Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed.