Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren's syndrome and systemic lupus erythematosus.
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).


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.
Sellam
Jérémie
J
Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
Miceli-Richard
Corinne
C
Gottenberg
Jacques-Eric
JE
Ittah
Marc
M
Lavie
Frédéric
F
Lacabaratz
Christine
C
Gestermann
Nicolas
N
Proust
Alexis
A
Lambotte
Olivier
O
Mariette
Xavier
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053264:B-Cell Activating Factor / Q000097:blood / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic
D053264:B-Cell Activating Factor; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins