title: Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients.
abstract: BACKGROUND
  Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD).
  
  
  METHODS
  Peripheral blood B cells were purified and activated by BCR with or without Toll-like receptor 9 (TLR9) stimulation in the presence or absence of epratuzumab. Cytokine production by B cells (interleukin [IL]-6, tumor necrosis factor [TNF]-α and IL-10) in the supernatant and the induction of IL-10(+) B cells from patients with SLE and HD were analyzed.
  
  
  RESULTS
  The secretion of the proinflammatory cytokines TNF-α and IL-6 by anti-BCR and BCR- and/or TLR9-activated B cells from HD and patients with SLE was inhibited by epratuzumab. In contrast, the production of IL-10 by B cells was not affected by epratuzumab under either stimulation condition. Consistently, the induction of IL-10-producing B cells in culture was not affected by epratuzumab.
  
  
  CONCLUSIONS
  Epratuzumab, by targeting CD22, was able to inhibit the production of the proinflammatory cytokines IL-6 and TNF-α by B cells, in contrast to IL-10, in vitro. These data suggest that targeting CD22 alters the balance between proinflammatory cytokines (TNF-α, IL-6) and the regulatory cytokine IL-10 as another B cell effector mechanism.
authors.affiliation: Department Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, CC12, Charité Berlin, Charitéplatz 01, 10098, Berlin, Germany. vanessa.fleischer@gmx.de.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fleischer
authors.affiliation: Department Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, CC12, Charité Berlin, Charitéplatz 01, 10098, Berlin, Germany. julia.sieber@charite.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Sieber
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), Leibniz Institute, Berlin, Germany. fleischer@drfz.de.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Fleischer
authors.affiliation: UCB Celltech, Slough, UK. tony.Shock@ucb.com.
authors.forename: Anthony
authors.initials: A
authors.lastname: Shock
authors.affiliation: Department Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, CC12, Charité Berlin, Charitéplatz 01, 10098, Berlin, Germany. guido.heine@charite.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), Leibniz Institute, Berlin, Germany. capucine.daridon@gmail.com.
authors.forename: Capucine
authors.initials: C
authors.lastname: Daridon
authors.affiliation: Department Medicine/Rheumatology and Clinical Immunology, Charité University Medicine Berlin, CC12, Charité Berlin, Charitéplatz 01, 10098, Berlin, Germany. thomas.doerner@charite.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001782:Blood Donors; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D018836:Inflammation Mediators; D016753:Interleukin-10; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C508609:IL10 protein, human; C508600:IL6 protein, human; C439524:TNF protein, human; C448700:epratuzumab