title: 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.
  
  
  CONCLUSIONS
  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.affiliation: The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Yahata-nishi, Kitakyushu 807-8555, Japan. tanaka@med.uoeh-u.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Iwata
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.forename: Masao
authors.initials: M
authors.lastname: Nawata
authors.forename: Sonosuke
authors.initials: S
authors.lastname: Yukawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hanami
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Fukuyo
authors.forename: Ippei
authors.initials: I
authors.lastname: Miyagawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kubo
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D010641:Phenotype; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D007155:Immunologic Factors; D000069283:Rituximab