Down-regulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful treatment with rituximab.
OBJECTIVE
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T cells and polyclonally activated B cells that produce autoantibodies. Five SLE patients who failed to respond to conventional immunosuppressants were treated with anti-CD20 antibody (rituximab) and their clinical manifestations and laboratory data were evaluated, including phenotypic analysis of B cells.


METHODS
Rituximab (375 mg/m(2)) was administered weekly for 2 weeks in five SLE patients who developed severe manifestations despite intensive treatment.


RESULTS
Rituximab resulted in rapid improvement (within several days) in clinical manifestations such as consciousness disorder, seizures, progressive sensory disorder, haemolytic crisis, cardiac function and laboratory data. The effects lasted 20 months in one patient; other patients were in remission for more than 6 months. Flow cytometric analysis revealed down-regulation of CD40 and CD80 expression on CD19-positive B cells 1 week after infusion of rituximab, and such down-regulation was seen for more than 7 months in two patients.


CONCLUSIONS
Our pilot study provides sufficient evidence of excellent tolerability and high efficacy of rituximab therapy in refractory SLE. Rituximab not only reduced B-cell number and IgG levels but down-regulated CD40 and CD80 on B cells, suggesting possible disturbance of T-cell activation through these costimulatory molecules. Reduction of both quantity and quality of B cells suggests that rituximab could improve the disease course in patients with refractory SLE.
Tokunaga
M
M
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan.
Fujii
K
K
Saito
K
K
Nakayamada
S
S
Tsujimura
S
S
Nawata
M
M
Tanaka
Y
Y
D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018122:B7-1 Antigen; D019013:CD40 Antigens; D007074:Immunoglobulin G; D000069283:Rituximab