Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab

Shigeru Iwata, Kazuyoshi Saito, Mikiko Tokunaga, Kunihiro Yamaoka, Masao Nawata, Sonosuke Yukawa, Kentaro Hanami, Shunsuke Fukuyo, Ippei Miyagawa, Satoshi Kubo, Yoshiya Tanaka

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53 Citations (Scopus)

Abstract

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. The Journal of Rheumatology

Original languageEnglish
Pages (from-to)633-641
Number of pages9
JournalJournal of Rheumatology
Volume38
Issue number4
DOIs
Publication statusPublished - 2011 Apr 1

Keywords

  • B cell depletion therapy
  • Rituximab
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Iwata, S., Saito, K., Tokunaga, M., Yamaoka, K., Nawata, M., Yukawa, S., Hanami, K., Fukuyo, S., Miyagawa, I., Kubo, S., & Tanaka, Y. (2011). Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. Journal of Rheumatology, 38(4), 633-641. https://doi.org/10.3899/jrheum.100729