Resistance to exogenous TGF-ß effects in patients with systemic lupus erythematosus.
J Clin Immunol
; 31(4): 574-83, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21503670
ABSTRACT
BACKGROUND:
The mechanisms underlying the loss of self-tolerance in systemic lupus erythematosus (SLE) are incompletely deciphered. TGF-ß 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-ß receptor. The present work aims to define whether resistance to TGF-ß 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-ß1 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-ß1. The responses to the anti-proliferative and transcriptional effects of TGF-ß were, however, discordant in a high proportion of our patients. Hence, we distinguish three distinct profiles of resistance to TGF-ß1 and suggest that patients may exhibit different defects affecting distinct points of TGF-ß1 signaling pathways.CONCLUSION:
Our data demonstrate the presence of an impaired response of peripheral cells to TGF-ß1 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-ß1 in SLE.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Fator de Crescimento Transformador beta
/
Lúpus Eritematoso Sistêmico
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article