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Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren’s syndrome and systemic lupus erythematosus
  1. Jérémie Sellam1,
  2. Corinne Miceli-Richard1,
  3. Jacques-Eric Gottenberg1,
  4. Marc Ittah1,
  5. Frédéric Lavie1,
  6. Christine Lacabaratz2,
  7. Nicolas Gestermann2,
  8. Alexis Proust3,
  9. Olivier Lambotte2,
  10. Xavier Mariette
  1. 1Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
  2. 2Médecine Interne, INSERM U802 Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
  3. 3Institut Pour la Santé et la Recherche Médicale (INSERM) U802, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
  1. Correspondence to:
    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

Objective: To analyse B cell activating factor (BAFF) receptor (BAFF-R) expression on peripheral lymphocytes from patients with primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE).

Patients and methods: Peripheral blood mononuclear cells from 20 patients with pSS, 19 patients with SLE and 15 controls were examined by flow cytometry to investigate BAFF-R mean fluorescence intensity (MFI) on lymphocytes. BAFF-R mRNA level from isolated blood B cells of nine patients with pSS and eight controls was assessed by real-time quantitative reverse transcription-PCR. BAFF serum level was determined by ELISA.

Results: In all subjects, BAFF-R was expressed on all naïve CD27− and memory CD27+ B-cells and was present on <0.5% of T cells. The expression of BAFF-R on B cells was significantly decreased in patients with pSS as compared with controls (MFI = 7.8 vs 10.6, p = 0.001), and was intermediate in patients with SLE (MFI = 9.5). Serum BAFF level was inversely correlated with BAFF-R MFI (p = 0.007), but not because of competition between endogenous BAFF (at observed concentrations in patients) and the monoclonal antibody (11C1) detecting BAFF-R. BAFF-R mRNA levels did not differ between patients with pSS and controls (p = 0.48). BAFF-R MFI decreased after overnight culture with recombinant human BAFF (from 32.5 to 25.4, p = 0.03). Contrary to the serum BAFF level, BAFF-R expression was correlated with extraglandular involvement in pSS and SLE Disease Activity Index.

Conclusions: BAFF-R expression is reduced on peripheral B cells of patients with pSS and SLE. This down-regulation occurs through a post-transcriptional mechanism and could be the consequence of chronic increase in BAFF. BAFF-R levels on B cells could be a novel activity biomarker in autoimmune diseases.

  • AID, autoimmune disease
  • BAFF, B cell activating factor of the tumour necrosis factor family
  • BAFF-R, BAFF receptor
  • CE, cell equivalence
  • FACS, fluorescence-activated cell sorter
  • mAb, monoclonal antibodies
  • MFI, mean fluorescence intensity
  • PBMC, peripheral blood mononuclear cell
  • pSS, primary Sjögren’s syndrome
  • rhBAFF, recombinant human BAFF
  • SLE, systemic lupus erythematosus
  • SLEDAI, SLE Disease Activity Index

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Footnotes

  • Published Online First 21 December 2006

  • Funding: This work was supported by grants from Société Française de Rhumatologie, Fondation pour la Recherche Médicale.

  • Competing interests: None declared.

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