Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 in patients with eosinophilic disorders: Receptor expression and targeting using chimeric antibodies.
Animals
Antibodies, Blocking
/ genetics
Antigens, CD
/ genetics
Antigens, Differentiation, B-Lymphocyte
/ genetics
Cell Death
Cells, Cultured
Cytotoxicity, Immunologic
Eosinophilia
/ immunology
Eosinophils
/ immunology
Humans
Immunoglobulin G
/ genetics
Interleukin-5
/ metabolism
Killer Cells, Natural
/ immunology
Lectins
/ genetics
Leukocyte Count
Mice
Mice, SCID
Molecular Targeted Therapy
Recombinant Fusion Proteins
/ genetics
Transcriptome
Siglec-8
apoptosis
eosinophil
eosinophilic gastrointestinal disease
hypereosinophilic syndrome
inhibitory receptor
mast cell
mastocytosis
monoclonal antibody
soluble receptor
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
20
04
2018
revised:
19
09
2018
accepted:
26
10
2018
pubmed:
14
12
2018
medline:
6
5
2020
entrez:
14
12
2018
Statut:
ppublish
Résumé
Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 is selectively expressed on eosinophils, mast cells, and basophils and, when engaged on eosinophils, can cause cell death. We sought to characterize surface and soluble Siglec-8 (sSiglec-8) levels in normal donors (NDs) and eosinophilic donors (EOs) and assess the efficacy of anti-Siglec-8 antibodies in inducing eosinophil cell death in vitro. Eosinophil expression of Siglec-8 was assessed by using flow cytometry and quantitative PCR. Serum sSiglec-8 levels were measured by means of ELISA. Induction of eosinophil death by IgG Siglec-8 was consistently expressed on eosinophils from NDs and EOs and did not correlate with absolute eosinophil count or disease activity. sSiglec-8 levels were measurable in sera from most donors unrelated to absolute eosinophil counts or Siglec-8 surface expression. c2E2 IgG Siglec-8 is highly expressed on blood eosinophils from EOs and NDs and represents a potential therapeutic target for eosinophilic disorders. Enhanced killing of eosinophils in the presence of IL-5 might lead to increased efficacy in patients with IL-5-driven eosinophilia.
Sections du résumé
BACKGROUND
Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 is selectively expressed on eosinophils, mast cells, and basophils and, when engaged on eosinophils, can cause cell death.
OBJECTIVE
We sought to characterize surface and soluble Siglec-8 (sSiglec-8) levels in normal donors (NDs) and eosinophilic donors (EOs) and assess the efficacy of anti-Siglec-8 antibodies in inducing eosinophil cell death in vitro.
METHODS
Eosinophil expression of Siglec-8 was assessed by using flow cytometry and quantitative PCR. Serum sSiglec-8 levels were measured by means of ELISA. Induction of eosinophil death by IgG
RESULTS
Siglec-8 was consistently expressed on eosinophils from NDs and EOs and did not correlate with absolute eosinophil count or disease activity. sSiglec-8 levels were measurable in sera from most donors unrelated to absolute eosinophil counts or Siglec-8 surface expression. c2E2 IgG
CONCLUSIONS
Siglec-8 is highly expressed on blood eosinophils from EOs and NDs and represents a potential therapeutic target for eosinophilic disorders. Enhanced killing of eosinophils in the presence of IL-5 might lead to increased efficacy in patients with IL-5-driven eosinophilia.
Identifiants
pubmed: 30543818
pii: S0091-6749(18)31741-X
doi: 10.1016/j.jaci.2018.10.066
pmc: PMC6556424
mid: NIHMS1516349
pii:
doi:
Substances chimiques
Antibodies, Blocking
0
Antigens, CD
0
Antigens, Differentiation, B-Lymphocyte
0
Immunoglobulin G
0
Interleukin-5
0
Lectins
0
Recombinant Fusion Proteins
0
SIGLEC8 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2227-2237.e10Subventions
Organisme : NIAID NIH HHS
ID : U19 AI136443
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI097073
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK097721
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI072265
Pays : United States
Informations de copyright
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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