Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis.
B cell depletion may affect T cell activation and costimulation status in rituximab-treated patients with SLE. We examined whether rituximab administration in patients with active lupus nephritis is related to changes in mRNA expression of genes that define regulatory T cells (Tregs) in peripheral blood lymphocytes, measured by real-time PCR. At the early phase of B cell depletion mRNA levels of CD25, CTLA-4, GITR and the bona fide Treg functional marker FOXP3 increased significantly in all 7 patients examined. In contrast, mRNA levels of the costimulatory/activation T cell molecule CD40L were profoundly reduced, while mRNA levels of TGF-beta, a cytokine contributing to Treg induction, increased significantly in all. During follow-up, increased FOXP3 mRNA persisted in those patients in clinical remission, while in those patients with active disease subsequent decreases were noted. Further studies should examine whether modulation of Tregs by therapeutic B cell depletion contributes and/or predicts lupus disease remission.
Sfikakis
P P
PP
First Department of Propedeutic and Internal Medicine, Athens University Medical School, 3, Amaryllidos Str, 15452, Athens, Greece. psfikakis@med.uoa.gr
Souliotis
V L
VL
Fragiadaki
K G
KG
Moutsopoulos
H M
HM
Boletis
J N
JN
Theofilopoulos
A N
AN
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects; D023201:CD40 Ligand / Q000187:drug effects / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000069283:Rituximab; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007155:Immunologic Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D023201:CD40 Ligand; D000069283:Rituximab