title: Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor.
abstract: BACKGROUND
  Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear.
  
  
  METHODS
  The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab.
  
  
  RESULTS
  RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD+CD27+ memory B cells than healthy individuals, whereas post-switch IgD-CD27+ accumulate with increased disease duration. Notably, both pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD+CD27 memory B cells in the peripheral blood.
  
  
  CONCLUSIONS
  The data suggest that decreases in peripheral blood IgD+CD27+ pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF.
authors.affiliation: Centro de Neurociências e Biologia Celular, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal. mmargarida.carneiro@gmail.com.
authors.forename: M Margarida
authors.initials: MM
authors.lastname: Souto-Carneiro
authors.forename: Vijayabhanu
authors.initials: V
authors.lastname: Mahadevan
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takada
authors.forename: Ruth
authors.initials: R
authors.lastname: Fritsch-Stork
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.forename: Margaret
authors.initials: M
authors.lastname: Brown
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: Mildred
authors.initials: M
authors.lastname: Wilson
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000097:blood; D007156:Immunologic Memory; D016130:Immunophenotyping; D000069285:Infliximab; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab