Biomaterial Database

BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome. 2007

Jacques-Olivier Pers, and Valérie Devauchelle, and Capucine Daridon, and Boutahar Bendaoud, and Rozenn Le Berre, and Anne Bordron, and Pascal Hutin, and Yves Renaudineau, and Maryvonne Dueymes, and Séverine Loisel, and Christian Berthou, and Alain Saraux, and Pierre Youinou

Brest University Medical School, Brest, France.

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.

UI	MeSH Term	Description	Entries
D008212	Lymphocyte Depletion	Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.	Depletion, Lymphocyte
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069283	Rituximab	A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.	CD20 Antibody, Rituximab,GP2013,IDEC-C2B8,IDEC-C2B8 Antibody,Mabthera,Rituxan,IDEC C2B8,IDEC C2B8 Antibody,Rituximab CD20 Antibody
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D001706	Biopsy	Removal and pathologic examination of specimens from the living body.	Biopsies
D012469	Salivary Glands	Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND).	Gland, Salivary,Glands, Salivary,Salivary Gland
D012859	Sjogren's Syndrome	Chronic inflammatory and autoimmune disease in which the salivary and lacrimal glands undergo progressive destruction by lymphocytes and plasma cells resulting in decreased production of saliva and tears. The primary form, often called sicca syndrome, involves both KERATOCONJUNCTIVITIS SICCA and XEROSTOMIA. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis.	Sicca Syndrome,Sjogren Syndrome,Sjogrens Syndrome,Syndrome, Sicca,Syndrome, Sjogren's
D016175	B-Lymphocyte Subsets	A classification of B-lymphocytes based on structurally or functionally different populations of cells.	B-Cell Subsets,Tumor-Infiltrating B Cells,Tumor-Infiltrating B Lymphocytes,B Effector 1 Cells,B Effector 2 Cells,B-1 Cells,B-1 Lymphocytes,B-2 Lymphocytes,B-Lymphocytes, Effector,B1 Lymphocytes,B2 Lymphocytes,Be1 Cells,Be2 Cells,Effector B Cells,B 1 Cells,B 1 Lymphocytes,B 2 Lymphocytes,B Cell Subsets,B Cell, Tumor-Infiltrating,B Lymphocyte Subsets,B Lymphocyte, Tumor-Infiltrating,B-1 Cell,B-1 Lymphocyte,B-2 Lymphocyte,B-Cell Subset,B-Lymphocyte Subset,B-Lymphocyte, Effector,B1 Lymphocyte,B2 Lymphocyte,Be1 Cell,Be2 Cell,Cell, B-1,Cell, Be1,Cell, Be2,Effector B Cell,Effector B-Lymphocyte,Effector B-Lymphocytes,Lymphocyte, B-1,Lymphocyte, B-2,Lymphocyte, B1,Lymphocyte, B2,Tumor Infiltrating B Cells,Tumor Infiltrating B Lymphocytes,Tumor-Infiltrating B Cell,Tumor-Infiltrating B Lymphocyte