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

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.

• Authors: Shigeru Iwata, Kazuyoshi Saito, Mikiko Tokunaga, Kunihiro Yamaoka, Masao Nawata, Sonosuke Yukawa, Kentaro Hanami, Shunsuke Fukuyo, Ippei Miyagawa, Satoshi Kubo, Yoshiya Tanaka
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 38 Issue 4 Pg. 633-41 (Apr 2011) ISSN: 0315-162X [Print] Canada
• PMID: 21159836 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antigens, CD
• Immunologic Factors
• Rituximab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal, Murine-Derived (pharmacology, therapeutic use)
• Antigens, CD (immunology)
• B-Lymphocytes (cytology, drug effects, immunology)
• Cell Differentiation
• Cohort Studies
• Female
• Humans
• Immunologic Factors (pharmacology, therapeutic use)
• Lupus Erythematosus, Systemic (blood, drug therapy, immunology, prevention & control)
• Lymphocyte Depletion (methods)
• Male
• Phenotype
• Recurrence
• Remission Induction
• Rituximab
• T-Lymphocytes (cytology, drug effects, immunology)
• Young Adult