BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome.
Arthritis Rheum
; 56(5): 1464-77, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17469105
ABSTRACT
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.CONCLUSION:
The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.
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Bases de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Síndrome de Sjogren
/
Antirreumáticos
/
Fator Ativador de Células B
/
Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Arthritis Rheum
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França