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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.

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Authors and Affiliations

  1. Department of Clinical Immunology, Institut Pasteur de Tunis, 13, Place Pasteur, 1002 Le Belvédère, Tunis, Tunisia

    Asma Elbeldi-Ferchiou, Mélika Ben Ahmed, Maha Abdeladhim, Nadia Belhadj Hmida & Hechmi Louzir

  2. Tunis-El Manar University, Tunis, Tunisia

    Asma Elbeldi-Ferchiou, Mélika Ben Ahmed, Monia Smiti-Khanfir, Mohamed Habib Houman, Maha Abdeladhim, Nadia Belhadj Hmida & Hechmi Louzir

  3. Department of Internal Medicine, La Rabta Hospital, Tunis, Tunisia

    Monia Smiti-Khanfir & Mohamed Habib Houman

  4. INSERM, U989, Paris, France

    Nadine Cerf-Bensussan

  5. Faculté de Médecine, Université Paris Descartes, Paris, France

    Nadine Cerf-Bensussan

Authors
  1. Asma Elbeldi-Ferchiou
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  2. Mélika Ben Ahmed
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Correspondence to Mélika Ben Ahmed.

Additional information

Asma Elbeldi-Ferchiou and Mélika Ben Ahmed contributed equally to this work.

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Elbeldi-Ferchiou, A., Ben Ahmed, M., Smiti-Khanfir, M. et al. Resistance to Exogenous TGF-β Effects in Patients with Systemic Lupus Erythematosus. J Clin Immunol 31, 574–583 (2011). https://doi.org/10.1007/s10875-011-9531-9

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  • DOI: https://doi.org/10.1007/s10875-011-9531-9

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