RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP 633
OP 641
DO 10.3899/jrheum.100729
VO 38
IS 4
A1 SHIGERU IWATA
A1 KAZUYOSHI SAITO
A1 MIKIKO TOKUNAGA
A1 KUNIHIRO YAMAOKA
A1 MASAO NAWATA
A1 SONOSUKE YUKAWA
A1 KENTARO HANAMI
A1 SHUNSUKE FUKUYO
A1 IPPEI MIYAGAWA
A1 SATOSHI KUBO
A1 YOSHIYA TANAKA
YR 2011
UL http://www.jrheum.org/content/38/4/633.abstract
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.