Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus. - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Immunology Year : 2011

Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus.

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Abstract

BACKGROUND: The mechanisms underlying the loss of self-tolerance in systemic lupus erythematosus (SLE) are incompletely deciphered. TGF-β plays a key role in self-tolerance demonstrated by the onset of a fatal autoimmune syndrome associated with lupus autoantibodies in mice lacking a functional TGF-β receptor. The present work aims to define whether resistance to TGF-β might contribute to the pathogenesis of SLE. METHODS: Twenty-two patients with active SLE, 16 with other connective tissue diseases, and 10 healthy controls were prospectively included in this study. The effects of exogenous TGF-β1 on IL-2-dependent T-cell proliferation, IFN-γ secretion, and target gene transcription were analyzed on peripheral blood mononuclear cells. RESULTS: Our results showed that 75% of patients with SLE or other connective tissue diseases were totally or partially resistant to the effects of TGF-β1. The responses to the anti-proliferative and transcriptional effects of TGF-β were, however, discordant in a high proportion of our patients. Hence, we distinguish three distinct profiles of resistance to TGF-β1 and suggest that patients may exhibit different defects affecting distinct points of TGF-β1 signaling pathways. CONCLUSION: Our data demonstrate the presence of an impaired response of peripheral cells to TGF-β1 in patients with active SLE that may participate to the pathogenesis of the disease. Further studies will be necessary to delineate the mechanisms underlying the lymphocyte resistance to TGF-β1 in SLE.

Dates and versions

pasteur-00606434 , version 1 (06-07-2011)

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Asma Elbeldi-Ferchiou, Mélika Ben Ahmed, Monia Smiti-Khanfir, Mohamed Habib Houman, Maha Abdeladhim, et al.. Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus.. Journal of Clinical Immunology, 2011, epub ahead of print. ⟨10.1007/s10875-011-9531-9⟩. ⟨pasteur-00606434⟩
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