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Arthritis Res Ther ; 14(5): R200, 2012 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-23006144

RESUMEN

INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown. METHODS: Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively. RESULTS: IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept. CONCLUSIONS: Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.


Asunto(s)
Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Interleucinas/metabolismo , Proteínas Recombinantes de Fusión/uso terapéutico , Piel/metabolismo , Membrana Sinovial/metabolismo , Adulto , Alefacept , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Artritis Psoriásica/metabolismo , Artritis Psoriásica/patología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Biopsia , Antígenos CD55/metabolismo , Fármacos Dermatológicos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes de Fusión/farmacología , Piel/efectos de los fármacos , Piel/patología , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/patología , Factores de Tiempo , Resultado del Tratamiento
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