BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration and the production of autoantibodies, leading to the destruction of lacrimal and salivary glands. However, very little is known about the pathogenesis of the disorder. CD70 (TNFSF7), a B cell costimulatory molecule, is overexpressed in CD4(+) T cells from patients with systemic erythematosus lupus (SLE) due to the hypomethylation of its promoter. OBJECTIVE: In this study we asked whether the epigenetic regulation of CD70 expression is abnormal in pSS. METHODS: CD70 levels in CD4(+) T cells from pSS patients, tinea pedis and healthy controls were measured by real-time RT-PCR and flow cytometry. Bisulphite sequencing was performed to determine the methylation status of the TNFSF7 promoter region. RESULTS: CD70 expression was significantly elevated and correlated with a decrease in TNFSF7 promoter methylation in pSS CD4(+) T cells compared to controls. CONCLUSIONS: Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4(+) T cells, and may contribute to autoreactivity. Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration and the production of autoantibodies, leading to the destruction of lacrimal and salivary glands. However, very little is known about the pathogenesis of the disorder. CD70 (TNFSF7), a B cell costimulatory molecule, is overexpressed in CD4(+) T cells from patients with systemic erythematosus lupus (SLE) due to the hypomethylation of its promoter. OBJECTIVE: In this study we asked whether the epigenetic regulation of CD70 expression is abnormal in pSS. METHODS:CD70 levels in CD4(+) T cells from pSS patients, tinea pedis and healthy controls were measured by real-time RT-PCR and flow cytometry. Bisulphite sequencing was performed to determine the methylation status of the TNFSF7 promoter region. RESULTS:CD70 expression was significantly elevated and correlated with a decrease in TNFSF7 promoter methylation in pSS CD4(+) T cells compared to controls. CONCLUSIONS: Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4(+) T cells, and may contribute to autoreactivity. Copyright 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Authors: Chary López-Pedrera; Carlos Pérez-Sánchez; Manuel Ramos-Casals; Monica Santos-Gonzalez; Antonio Rodriguez-Ariza; Ma José Cuadrado Journal: Clin Dev Immunol Date: 2011-09-14