[Sequential histological and immunohistochemical assessment of proliferation and apoptotic markers during treatment of psoriasis with antitumor necrosis factor alpha (infliximab)].
OBJECTIVE
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.


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.
Gómez-Mateo
C
C
Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, España.
Avalos-Peralta
S P
SP
Ríos-Martín
J J
JJ
Carrizosa-Esquivel
A M
AM
González-Cámpora
R
R
Camacho-Martínez
F
F
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab