Original article
Sequential Histological and Immunohistochemical Assessment of Proliferation and Apoptotic Markers During Treatment of Psoriasis With Antitumor Necrosis Factor α (Infliximab)
Evaluación Histológica e Inmunohistoquímica Secuencial Demarcadores de Proliferación y Apoptosis Durante El Tratamiento de la Psoriasis con Anti-factor de Necrosis Tumoral α (Infliximab)
C. Gómez-Mateoa, S.P. Ávalos-Peraltab, J.J. Ríos-Martína,
, A.M. Carrizosa-Esquivelb, R. González-Cámporaa, F. Camacho-Martínezb
Autor para correspondencia
jjrios@ono.com
Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain.
Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain.
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Marcoval" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J.R." "apellidos" => "Ferreres" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Moreno" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Marcoval" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219009700873?idApp=UINPBA000044" "url" => "/15782190/0000010000000005/v1_201304241456/S1578219009700873/v1_201304241456/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Sequential Histological and Immunohistochemical Assessment of Proliferation and Apoptotic Markers During Treatment of Psoriasis With Antitumor Necrosis Factor α (Infliximab)" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "420" "paginaFinal" => "424" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Gómez-Mateo, S.P. Ávalos-Peralta, J.J. Ríos-Martín, A.M. Carrizosa-Esquivel, R. González-Cámpora, F. Camacho-Martínez" "autores" => array:6 [ 0 => array:3 [ "nombre" => "C." "apellidos" => "Gómez-Mateo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "S.P." "apellidos" => "Ávalos-Peralta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 2 => array:4 [ "nombre" => "J.J." "apellidos" => "Ríos-Martín" "email" => array:1 [ 0 => "jjrios@ono.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 3 => array:3 [ "nombre" => "A.M." "apellidos" => "Carrizosa-Esquivel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 4 => array:3 [ "nombre" => "R." "apellidos" => "González-Cámpora" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 5 => array:3 [ "nombre" => "F." "apellidos" => "Camacho-Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Seville, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Virgen Macarena, Seville, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación Histológica e Inmunohistoquímica Secuencial Demarcadores de Proliferación y Apoptosis Durante El Tratamiento de la Psoriasis con Anti-factor de Necrosis Tumoral α (Infliximab)" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaAceptado" => "2008-10-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec84486" "palabras" => array:5 [ 0 => "psoriasis" 1 => "tumor necrosis factor a" 2 => "histology" 3 => "immunohistochemistry" 4 => "apoptosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec84485" "palabras" => array:5 [ 0 => "psoriasis" 1 => "tumor necrosis factor a" 2 => "histology" 3 => "immunohistochemistry" 4 => "apoptosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background and objectives</span><p class="elsevierStyleSimplePara elsevierViewall">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) a 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.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Introducción y objetivos</span><p class="elsevierStyleSimplePara elsevierViewall">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 a (TNF-a) (infliximab) ha proporcionado respuestas clínicas significativas; sin embargo, los mecanismos implicados en 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.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">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–.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">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 2 8 días.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La respuesta clínica e histológica de la psoriasis con infliximab no se asoció a un incremento significativo en los marcadores de apoptosis evaluados.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunopathogenic mechanisms in psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.E. Gudjonsson" 1 => "A. Johnston" 2 => "H. Sigmundsdottur" 3 => "H. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 1 | 0 | 1 |
| 2024 Octubre | 55 | 52 | 107 |
| 2024 Septiembre | 59 | 31 | 90 |
| 2024 Agosto | 93 | 67 | 160 |
| 2024 Julio | 64 | 36 | 100 |
| 2024 Junio | 68 | 39 | 107 |
| 2024 Mayo | 49 | 35 | 84 |
| 2024 Abril | 58 | 42 | 100 |
| 2024 Marzo | 53 | 37 | 90 |
| 2024 Febrero | 49 | 39 | 88 |
| 2024 Enero | 34 | 47 | 81 |
| 2023 Diciembre | 35 | 39 | 74 |
| 2023 Noviembre | 35 | 45 | 80 |
| 2023 Octubre | 35 | 30 | 65 |
| 2023 Septiembre | 34 | 39 | 73 |
| 2023 Agosto | 30 | 20 | 50 |
| 2023 Julio | 36 | 41 | 77 |
| 2023 Junio | 28 | 32 | 60 |
| 2023 Mayo | 34 | 23 | 57 |
| 2023 Abril | 28 | 22 | 50 |
| 2023 Marzo | 19 | 29 | 48 |
| 2023 Febrero | 19 | 26 | 45 |
| 2023 Enero | 24 | 35 | 59 |
| 2022 Diciembre | 23 | 52 | 75 |
| 2022 Noviembre | 17 | 28 | 45 |
| 2022 Octubre | 13 | 26 | 39 |
| 2022 Septiembre | 15 | 36 | 51 |
| 2022 Agosto | 17 | 37 | 54 |
| 2022 Julio | 18 | 40 | 58 |
| 2022 Junio | 15 | 30 | 45 |
| 2022 Mayo | 43 | 42 | 85 |
| 2022 Abril | 26 | 40 | 66 |
| 2022 Marzo | 31 | 58 | 89 |
| 2022 Febrero | 34 | 28 | 62 |
| 2022 Enero | 54 | 49 | 103 |
| 2021 Diciembre | 38 | 39 | 77 |
| 2021 Noviembre | 25 | 46 | 71 |
| 2021 Octubre | 34 | 50 | 84 |
| 2021 Septiembre | 15 | 43 | 58 |
| 2021 Agosto | 13 | 41 | 54 |
| 2021 Julio | 20 | 45 | 65 |
| 2021 Junio | 18 | 38 | 56 |
| 2021 Mayo | 23 | 29 | 52 |
| 2021 Abril | 43 | 84 | 127 |
| 2021 Marzo | 44 | 26 | 70 |
| 2021 Febrero | 53 | 31 | 84 |
| 2021 Enero | 31 | 13 | 44 |
| 2020 Diciembre | 27 | 18 | 45 |
| 2020 Noviembre | 23 | 19 | 42 |
| 2020 Octubre | 28 | 8 | 36 |
| 2020 Septiembre | 29 | 14 | 43 |
| 2020 Agosto | 24 | 27 | 51 |
| 2020 Julio | 15 | 5 | 20 |
| 2020 Junio | 19 | 28 | 47 |
| 2020 Mayo | 18 | 18 | 36 |
| 2020 Abril | 25 | 18 | 43 |
| 2020 Marzo | 19 | 21 | 40 |
| 2020 Febrero | 1 | 3 | 4 |
| 2020 Enero | 0 | 7 | 7 |
| 2019 Diciembre | 0 | 8 | 8 |
| 2019 Noviembre | 0 | 5 | 5 |
| 2019 Octubre | 0 | 2 | 2 |
| 2019 Septiembre | 0 | 1 | 1 |
| 2019 Agosto | 0 | 1 | 1 |
| 2019 Julio | 0 | 9 | 9 |
| 2019 Junio | 0 | 6 | 6 |
| 2019 Mayo | 1 | 59 | 60 |
| 2019 Abril | 1 | 12 | 13 |
| 2019 Marzo | 0 | 5 | 5 |
| 2019 Febrero | 0 | 3 | 3 |
| 2019 Enero | 0 | 4 | 4 |
| 2018 Marzo | 0 | 6 | 6 |
| 2018 Febrero | 10 | 9 | 19 |
| 2018 Enero | 16 | 18 | 34 |
| 2017 Diciembre | 16 | 15 | 31 |
| 2017 Noviembre | 16 | 16 | 32 |
| 2017 Octubre | 14 | 18 | 32 |
| 2017 Septiembre | 22 | 10 | 32 |
| 2017 Agosto | 25 | 21 | 46 |
| 2017 Julio | 30 | 9 | 39 |
| 2017 Junio | 45 | 25 | 70 |
| 2017 Mayo | 41 | 38 | 79 |
| 2017 Abril | 43 | 26 | 69 |
| 2017 Marzo | 22 | 20 | 42 |
| 2017 Febrero | 13 | 18 | 31 |
| 2017 Enero | 13 | 17 | 30 |
| 2016 Diciembre | 26 | 5 | 31 |
| 2016 Noviembre | 22 | 11 | 33 |
| 2016 Octubre | 25 | 25 | 50 |
| 2016 Septiembre | 32 | 20 | 52 |
| 2016 Agosto | 27 | 15 | 42 |
| 2016 Julio | 36 | 8 | 44 |
| 2016 Junio | 8 | 5 | 13 |
| 2016 Mayo | 12 | 22 | 34 |
| 2016 Abril | 5 | 6 | 11 |
| 2016 Marzo | 4 | 14 | 18 |
| 2016 Febrero | 6 | 8 | 14 |
| 2016 Enero | 5 | 12 | 17 |
| 2015 Diciembre | 9 | 8 | 17 |
| 2015 Noviembre | 10 | 9 | 19 |
| 2015 Octubre | 6 | 12 | 18 |
| 2015 Septiembre | 17 | 4 | 21 |
| 2015 Agosto | 20 | 6 | 26 |
| 2015 Julio | 27 | 13 | 40 |
| 2015 Junio | 30 | 14 | 44 |
| 2015 Mayo | 60 | 21 | 81 |
| 2015 Abril | 50 | 15 | 65 |
| 2015 Marzo | 27 | 14 | 41 |
| 2015 Febrero | 22 | 19 | 41 |
| 2015 Enero | 19 | 20 | 39 |
| 2014 Diciembre | 22 | 22 | 44 |
| 2014 Noviembre | 15 | 26 | 41 |
| 2014 Octubre | 30 | 26 | 56 |
| 2014 Septiembre | 29 | 28 | 57 |
| 2014 Agosto | 32 | 18 | 50 |
| 2014 Julio | 34 | 23 | 57 |
| 2014 Junio | 33 | 13 | 46 |
| 2014 Mayo | 44 | 12 | 56 |
| 2014 Abril | 43 | 12 | 55 |
| 2014 Marzo | 38 | 21 | 59 |
| 2014 Febrero | 24 | 24 | 48 |
| 2014 Enero | 33 | 21 | 54 |
| 2013 Diciembre | 36 | 17 | 53 |
| 2013 Noviembre | 31 | 23 | 54 |
| 2013 Octubre | 36 | 22 | 58 |
| 2013 Septiembre | 29 | 19 | 48 |
| 2013 Agosto | 16 | 32 | 48 |
| 2013 Julio | 41 | 37 | 78 |
| 2013 Junio | 31 | 39 | 70 |
| 2013 Mayo | 32 | 18 | 50 |
| 2013 Abril | 31 | 36 | 67 |
| 2013 Marzo | 34 | 26 | 60 |
| 2013 Febrero | 38 | 15 | 53 |
| 2013 Enero | 8 | 6 | 14 |
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