PT  - JOURNAL ARTICLE
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
TI  - Phenotypic Changes of Lymphocytes in Patients with Systemic Lupus Erythematosus Who Are in Longterm Remission After B Cell Depletion Therapy with Rituximab
AID  - 10.3899/jrheum.100729
DP  - 2011 Apr 01
TA  - The Journal of Rheumatology
PG  - 633--641
VI  - 38
IP  - 4
4099  - http://www.jrheum.org/content/38/4/633.short
4100  - http://www.jrheum.org/content/38/4/633.full
SO  - J Rheumatol2011 Apr 01; 38
AB  - 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.