BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of RITUXIMAB-TREATED patients with Sjögren's syndrome
Article first published online: 27 APR 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 5, pages 1464–1477, May 2007
How to Cite
Pers, J.-O., Devauchelle, V., Daridon, C., Bendaoud, B., Berre, R. L., Bordron, A., Hutin, P., Renaudineau, Y., Dueymes, M., Loisel, S., Berthou, C., Saraux, A. and Youinou, P. (2007), BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of RITUXIMAB-TREATED patients with Sjögren's syndrome. Arthritis & Rheumatism, 56: 1464–1477. doi: 10.1002/art.22603
- Issue published online: 27 APR 2007
- Article first published online: 27 APR 2007
- Manuscript Accepted: 14 FEB 2007
- Manuscript Received: 1 SEP 2006
- Association Française du Gougerot-Sjögren et des Syndromes Secs
- 2003 Clinical Research Hospital Program (PHRC 2003)
Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab.
A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients.
Baseline serum levels of BAFF correlated inversely (r = −0.92, P < 5 × 10−4) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5−,IgD−,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/−,IgD+,CD38+/−), and memory B cells (CD19+,CD5−,IgD−,CD38−). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally.
The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.