TY - JOUR T1 - Phenotypic Changes of Lymphocytes in Patients with Systemic Lupus Erythematosus Who Are in Longterm Remission After B Cell Depletion Therapy with Rituximab JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.100729 SP - jrheum.100729 AU - Shigeru Iwata AU - Kazuyoshi Saito AU - Mikiko Tokunaga AU - Kunihiro Yamaoka AU - Masao Nawata AU - Sonosuke Yukawa AU - Kentaro Hanami AU - Shunsuke Fukuyo AU - Ippei Miyagawa AU - Satoshi Kubo AU - Yoshiya Tanaka Y1 - 2010/12/15 UR - http://www.jrheum.org/content/early/2010/12/12/jrheum.100729.abstract N2 - 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. ER -