Journal
JOURNAL OF RHEUMATOLOGY
Volume 38, Issue 4, Pages 633-641Publisher
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.100729
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; RITUXIMAB; B CELL DEPLETION THERAPY
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Funding
- Ministry of Health, Labor and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- University of Occupational and Environmental Health, Japan
- Mitsubishi-Tanabe Pharma
- Pfizer Inc.
- Takeda Pharmaceutical Co. Ltd.
- Abbott
- Eisai Pharma
- Chugai Pharma
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Objective. Rituximab has recently emerged as a novel treatment strategy for systemic lupus erythematosus (SLE). We investigated longitudinally the differentiation and phenotypic changes of peripheral B cells and T cells in patients with SLE after rituximab treatment. Methods. Phenotypic changes on B cells and T cells in 10 patients with SLE treated with rituximab were analyzed before, 28 days after, and 2 years after rituximab treatment, and at relapse. Results. Rituximab rapidly depleted naive and memory B cells from the peripheral blood. In the patients with prolonged remission, the memory B cells remained depleted while naive B cells recovered within 3-9 months, and the expression levels of CD40 and CD80 remained downregulated for 2 years. There was also a decrease of memory T cells relative to naive T cells, and the expression of CD40L and inducible costimulator (ICOS) on CD4-positive T cells rapidly decreased and remained downregulated for 2 years. In 1 patient, an increase in the number of memory B cells with upregulation of CD40 and CD80 expression was noted just before relapse. In another patient with relapse, however, recovery of CD4-positive memory T cells with upregulation of ICOS expression was noted, with no change in the number of memory B cells. Conclusion. Our results suggest that the phenotypic changes of peripheral B cells result in inhibition of T cell differentiation and activation mediated by B cells and thereby bring about longterm remission of SLE. Activated memory B cells or ICOS-positive CD4-positive memory T cells reappeared in association with relapse, probably reflecting the heterogeneity of SLE. (First Release Dec 15 2010; J Rheumatol 2011;38:633-41; doi:10.3899/jrheum.100729)
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