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Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus.
MedLine Citation:
PMID:  21503670     Owner:  NLM     Status:  Publisher    
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.
Asma Elbeldi-Ferchiou; Mélika Ben Ahmed; Monia Smiti-Khanfir; Mohamed Habib Houman; Maha Abdeladhim; Nadia Belhadj Hmida; Nadine Cerf-Bensussan; Hechmi Louzir
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-19
Journal Detail:
Title:  Journal of clinical immunology     Volume:  -     ISSN:  1573-2592     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102137     Medline TA:  J Clin Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Clinical Immunology, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Le Belvédère, Tunis, Tunisia.
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