Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production.
BACKGROUND
The cytokine B cell-activating factor of the TNF family (BAFF) is involved in the pathogenesis of autoimmune diseases.


OBJECTIVE
To access changes in serum protein and mRNA levels of BAFF after rituximab treatment.


METHODS
Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients (two with lupus, two with Sjögren's syndrome, one with rheumatoid arthritis) before and 12 weeks (range 7-17) after a first course of rituximab infusion. Monocytes and B cells were selected from healthy controls and cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real-time PCR, respectively.


RESULTS
After rituximab treatment, median serum BAFF protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In monocytes cocultured with autologous B cells, BAFF protein level decreased, whereas the mRNA level was stable. In one closely monitored patient, the mRNA ratio of BAFF to actin in PBMCs increased later than the BAFF serum level.


CONCLUSIONS
Two distinct mechanisms are probably involved in the increase in BAFF level after B cell depletion: (1) the decrease in its receptors leading to a release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could favour the re-emergence of autoreactive B cells.
Lavie
Frédéric
F
Rheumatology Department, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Institut Pour la Santé et la Recherche Médicale (INSERM) U802, Université Paris-Sud 11, Le Kremlin Bicêtre, France.
Miceli-Richard
Corinne
C
Ittah
Marc
M
Sellam
Jérémie
J
Gottenberg
Jacques-Eric
JE
Mariette
Xavier
X
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000097:blood; D000069283:Rituximab; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D007155:Immunologic Factors; D012333:RNA, Messenger; D000069283:Rituximab