title: Resistance to exogenous TGF-β effects in patients with systemic lupus erythematosus.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Immunology, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Le Belvédère, Tunis, Tunisia.
authors.forename: Asma
authors.initials: A
authors.lastname: Elbeldi-Ferchiou
authors.forename: Mélika
authors.initials: M
authors.lastname: Ben Ahmed
authors.forename: Monia
authors.initials: M
authors.lastname: Smiti-Khanfir
authors.forename: Mohamed Habib
authors.initials: MH
authors.lastname: Houman
authors.forename: Maha
authors.initials: M
authors.lastname: Abdeladhim
authors.forename: Nadia
authors.initials: N
authors.lastname: Belhadj Hmida
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Hechmi
authors.initials: H
authors.lastname: Louzir
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D007376:Interleukin-2; D018125:Receptors, Transforming Growth Factor beta; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma