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Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production
  1. Frédéric Lavie,
  2. Corinne Miceli-Richard,
  3. Marc Ittah,
  4. Jérémie Sellam,
  5. Jacques-Eric Gottenberg,
  6. Xavier Mariette
  1. Rheumatology Department, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Institut Pour la Santé et la Recherche Médicale (INSERM) U802, Université Paris-Sud 11, Le Kremlin Bicêtre, France
  1. Correspondence to:
    Professor X Mariette
    Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France; xavier.mariette{at}bct.ap-hop-paris.fr

Abstract

Background: The cytokine B cell-activating factor of the TNF family (BAFF) is involved in the pathogenesis of autoimmune diseases.

Objective: To access changes in serum protein and mRNA levels of BAFF after rituximab treatment.

Methods: Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients (two with lupus, two with Sjögren’s syndrome, one with rheumatoid arthritis) before and 12 weeks (range 7–17) after a first course of rituximab infusion. Monocytes and B cells were selected from healthy controls and cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real-time PCR, respectively.

Results: After rituximab treatment, median serum BAFF protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In monocytes cocultured with autologous B cells, BAFF protein level decreased, whereas the mRNA level was stable. In one closely monitored patient, the mRNA ratio of BAFF to actin in PBMCs increased later than the BAFF serum level.

Conclusions: Two distinct mechanisms are probably involved in the increase in BAFF level after B cell depletion: (1) the decrease in its receptors leading to a release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could favour the re-emergence of autoreactive B cells.

  • BLyS, B lymphocyte stimulator
  • MALT, mucosa-associated lymphoid tissue
  • PBMC, peripheral blood mononuclear cells
  • pSS, primary Sjögren’s syndrome
  • RA, rheumatoid arthritis
  • SLE, systemic lupus erythematosus

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