title: Characterization of 5C11-positive activated interferon-producing cells in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  5C11 antibody is a novel monoclonal antibody against human BST2 and can be used to detect activation of interferon-producing cells (IPCs). Activated IPCs, which produce large amounts of interferon-α (IFNα), are considered to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). We investigated the characterization of 5C11-positive cells in patients with SLE.
  
  
  METHODS
  The proportions of 5C11-positive cells among blood dendritic cell antigen 2 (BDCA-2)-, CD3-, CD19- and CD14-positive cells in peripheral blood from SLE patients (SLE-PBMCs) and healthy controls (control-PBMCs) were analyzed by flow cytometry. The effect of 5C11 antibody on IFNα production from SLE-PBMCs under stimulation with cytosine-phosphate-guanosine (CpG2216, bacterial oligonucleotide motif) was also examined by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The proportions of 5C11-positive cells among BDCA-2-, CD3- and CD19-, but not CD14-positive cells in SLE-PBMCs were significantly increased compared to those in control-PBMCs (p < 0.0001, all). Especially, the number of 5C11-positive cells among BDCA-2-positive cells was significantly increased in SLE-PBMCs by about six-fold compared to that in control-PBMCs (p < 0.0001). 5C11 antibody inhibited IFNα production by SLE-PBMCs induced by CpG and the inhibition rates was 27% (p < 0.001).
  
  
  CONCLUSIONS
  SLE patients had a significantly higher proportion of 5C11-positive cells among CD3 and CD19 cells, and especially BDCA-2 positive cells. The ability of 5C11 antibody to inhibit IFNα production from SLE-PBMCs warrants further investigation for its possible clinical application for the treatment of SLE.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohshima
authors.forename: H
authors.initials: H
authors.lastname: Kanda
authors.forename: K
authors.initials: K
authors.lastname: Kubo
authors.forename: A
authors.initials: A
authors.lastname: Yonezumi-Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Tateishi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018941:Antigens, CD19 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists; D055815:Young Adult; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D015415:Biomarkers; D017252:CD3 Complex; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D051217:Toll-Like Receptor 9; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C443299:CLEC4C protein, human; C526902:CpG ODN 2216