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

Research output: Contribution to journalArticle

51 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
Externally publishedYes

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Cell- and Tissue-Based Therapy
Systemic Lupus Erythematosus
B-Lymphocytes
Lymphocytes
T-Lymphocytes
Inducible T-Cell Co-Stimulator Protein
Recurrence
Up-Regulation
Down-Regulation
Rituximab
CD40 Ligand
Rheumatology
Cell Differentiation
Therapeutics

Keywords

  • B cell depletion therapy
  • Rituximab
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. / Iwata, Shigeru; Saito, Kazuyoshi; Tokunaga, Mikiko; Yamaoka, Kunihiro; Nawata, Masao; Yukawa, Sonosuke; Hanami, Kentaro; Fukuyo, Shunsuke; Miyagawa, Ippei; Kubo, Satoshi; Tanaka, Yoshiya.

In: Journal of Rheumatology, Vol. 38, No. 4, 04.2011, p. 633-641.

Research output: Contribution to journalArticle

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, vol. 38, no. 4, pp. 633-641. https://doi.org/10.3899/jrheum.100729
Iwata, Shigeru ; Saito, Kazuyoshi ; Tokunaga, Mikiko ; Yamaoka, Kunihiro ; Nawata, Masao ; Yukawa, Sonosuke ; Hanami, Kentaro ; Fukuyo, Shunsuke ; Miyagawa, Ippei ; Kubo, Satoshi ; Tanaka, Yoshiya. / Phenotypic changes of lymphocytes in patients with systemic lupus erythematosus who are in longterm remission after B cell depletion therapy with rituximab. In: Journal of Rheumatology. 2011 ; Vol. 38, No. 4. pp. 633-641.
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AU - Iwata, Shigeru

AU - Saito, Kazuyoshi

AU - Tokunaga, Mikiko

AU - Yamaoka, Kunihiro

AU - Nawata, Masao

AU - Yukawa, Sonosuke

AU - Hanami, Kentaro

AU - Fukuyo, Shunsuke

AU - Miyagawa, Ippei

AU - Kubo, Satoshi

AU - Tanaka, Yoshiya

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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. The Journal of Rheumatology

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. The Journal of Rheumatology

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