BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome.
OBJECTIVE
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.


METHODS
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.


RESULTS
Baseline serum levels of BAFF correlated inversely (r = -0.92, P < 5 x 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.


CONCLUSIONS
The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.
Pers
Jacques-Olivier
JO
Brest University Medical School, Brest, France.
Devauchelle
Valérie
V
Daridon
Capucine
C
Bendaoud
Boutahar
B
Le Berre
Rozenn
R
Bordron
Anne
A
Hutin
Pascal
P
Renaudineau
Yves
Y
Dueymes
Maryvonne
M
Loisel
Séverine
S
Berthou
Christian
C
Saraux
Alain
A
Youinou
Pierre
P
D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000097:blood / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000473:pathology; D001402:B-Lymphocytes / Q000473:pathology*; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D000069283:Rituximab; D012469:Salivary Glands / Q000276:immunology; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000473:pathology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D000069283:Rituximab