Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system.
OBJECTIVE
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious treatment-resistant phenotype of systemic lupus erythematosus. A standard treatment for NPSLE is not available. This report describes the clinical and laboratory tests of 10 patients with NPSLE before and after rituximab treatment, including changes in lymphocyte phenotypes.


METHODS
Rituximab was administered at different doses in 10 patients with refractory NPSLE, despite intensive treatment.


RESULTS
Treatment with rituximab resulted in rapid improvement of central nervous system-related manifestations, particularly acute confusional state. Rituximab also improved cognitive dysfunction, psychosis and seizure, and reduced the SLE Disease Activity Index Score at day 28 in all 10 patients. These effects lasted for >1 year in five patients. Flow cytometric analysis showed that rituximab down regulated CD40 and CD80 on B cells and CD40L, CD69 and inducible costimulator on CD4+ T cells.


CONCLUSIONS
Rituximab rapidly improved refractory NPSLE, as evident by resolution of various clinical signs and symptoms and improvement of radiographic findings. The down regulation of functional molecules on B and T cells suggests that rituximab modulates the interaction of activated B and T cells through costimulatory molecules. These results warrant further analysis of rituximab as treatment for NPSLE.
Tokunaga
Mikiko
M
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka Yahata-nishi, Kitakyushu 807-8555 Japan.
Saito
Kazuyoshi
K
Kawabata
Daisuke
D
Imura
Yoshitaka
Y
Fujii
Takao
T
Nakayamada
Shingo
S
Tsujimura
Shizuyo
S
Nawata
Masao
M
Iwata
Shigeru
S
Azuma
Taeko
T
Mimori
Tsuneyo
T
Tanaka
Yoshiya
Y
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D020945:Lupus Vasculitis, Central Nervous System / Q000188:drug therapy* / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab