title: The eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1): a novel therapeutic target for eosinophilic disorders.
abstract: BACKGROUND
  Although several novel agents are currently in clinical trials for eosinophilic disorders, none has demonstrated efficacy in reducing blood and tissue eosinophilia in all subjects. Additional approaches are clearly needed.
  
  
  OBJECTIVE
  We sought to explore the potential of the human eosinophil surface receptor epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1) as a therapeutic target for eosinophilic disorders.
  
  
  METHODS
  EMR1 expression was assessed in blood and bone marrow specimens from eosinophilic and healthy subjects, cell lines, CD34(+) cells differentiated in vitro, and tissue biopsy specimens by using flow cytometry, quantitative PCR, and immunostaining. Eosinophil targeting by a novel, humanized, afucosylated anti-EMR1 IgG1 was evaluated in vitro by using a natural killer cell-mediated killing assay and in vivo in cynomolgus monkeys.
  
  
  RESULTS
  Analysis of blood and bone marrow cells from healthy and eosinophilic donors and in vitro-differentiated CD34(+) cells confirmed restriction of human EMR1 surface and mRNA expression to mature eosinophils. Tissue eosinophils also expressed EMR1. Although EMR1 was highly expressed on eosinophils from all subjects, surface expression was negatively correlated with absolute eosinophil counts (r = -0.46, P < .001), and soluble plasma levels correlated positively with absolute eosinophil counts (r = 0.69, P < .001), suggesting modulation of EMR1 in vivo. Nevertheless, afucosylated anti-EMR1 mAb dramatically enhanced natural killer cell-mediated killing of eosinophils from healthy and eosinophilic donors and induced a rapid and sustained depletion of eosinophils in monkeys.
  
  
  CONCLUSIONS
  EMR1 expression is restricted to mature blood and tissue eosinophils. Targeting of eosinophils with afucosylated anti-EMR1 antibody shows promise as a treatment for eosinophilic disorders.
authors: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md. Electronic address: legrandfa@niaid.nih.gov.
authors: Fanny
authors: F
authors: Legrand
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: Nenad
authors: N
authors: Tomasevic
authors: Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Md.
authors: Olga
authors: O
authors: Simakova
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
authors: Chyi-Chia Richard
authors: CC
authors: Lee
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
authors: Zengfang
authors: Z
authors: Wang
authors: Laboratory of Pathology, National Cancer Institute, Bethesda, Md.
authors: Mark
authors: M
authors: Raffeld
authors: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors: Michelle A
authors: MA
authors: Makiya
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: Varghese
authors: V
authors: Palath
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: John
authors: J
authors: Leung
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: Mark
authors: M
authors: Baer
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: Geoffrey
authors: G
authors: Yarranton
authors: Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Md.
authors: Irina
authors: I
authors: Maric
authors: KaloBios Pharmaceuticals, South San Francisco, Calif.
authors: Christopher
authors: C
authors: Bebbington
authors: Eosinophil Pathology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors: Amy D
authors: AD
authors: Klion
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002135:Calcium-Binding Proteins; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D020014:K562 Cells; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D009077:Mucins / Q000037:antagonists & inhibitors / Q000276:immunology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000276:immunology*; D020298:U937 Cells
chemical_list: C094471:ADGRE1 protein, human; D058846:Antibodies, Monoclonal, Murine-Derived; D002135:Calcium-Binding Proteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009077:Mucins; D043562:Receptors, G-Protein-Coupled
keywords: Epidermal growth factor–like module containing mucin-like hormone receptor 1; afucosylated antibody; eosinophil; eosinophilia; hypereosinophilic syndrome; mAb therapy