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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

Jérémie Sellam¹, Corinne Miceli-Richard¹, Jacques-Eric Gottenberg¹, Marc Ittah¹, Frédéric Lavie¹, Christine Lacabaratz², Nicolas Gestermann², Alexis Proust³, Olivier Lambotte², Xavier Mariette

¹ Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
² Médecine Interne, INSERM U802 Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Le Kremlin Bicêtre, France
³ Institut 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

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

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.

Abbreviations: 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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