Frontiers in Immunology (Nov 2019)
Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
- Lennard Ostendorf,
- Lennard Ostendorf,
- Lennard Ostendorf,
- Ronja Mothes,
- Ronja Mothes,
- Sofie van Koppen,
- Sofie van Koppen,
- Randall L. Lindquist,
- Randall L. Lindquist,
- Judith Bellmann-Strobl,
- Judith Bellmann-Strobl,
- Susanna Asseyer,
- Susanna Asseyer,
- Susanna Asseyer,
- Klemens Ruprecht,
- Klemens Ruprecht,
- Tobias Alexander,
- Raluca A. Niesner,
- Raluca A. Niesner,
- Anja E. Hauser,
- Anja E. Hauser,
- Friedemann Paul,
- Friedemann Paul,
- Friedemann Paul,
- Friedemann Paul,
- Helena Radbruch
Affiliations
- Lennard Ostendorf
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Lennard Ostendorf
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Lennard Ostendorf
- Immunodynamics, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany
- Ronja Mothes
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Ronja Mothes
- Biophysical Analysis, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany
- Sofie van Koppen
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Sofie van Koppen
- Biophysical Analysis, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany
- Randall L. Lindquist
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Randall L. Lindquist
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Judith Bellmann-Strobl
- NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Judith Bellmann-Strobl
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Susanna Asseyer
- NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Susanna Asseyer
- Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine & Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt – Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Susanna Asseyer
- Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom
- Klemens Ruprecht
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Klemens Ruprecht
- 0Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Tobias Alexander
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Raluca A. Niesner
- Biophysical Analysis, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany
- Raluca A. Niesner
- 1Fachbereich Veterinärmedizin, Institute of Veterinary Physiology, Freie Universität Berlin, Berlin, Germany
- Anja E. Hauser
- Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Anja E. Hauser
- Immunodynamics, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany
- Friedemann Paul
- NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Friedemann Paul
- Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Friedemann Paul
- Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine & Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt – Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Friedemann Paul
- 0Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- Helena Radbruch
- Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
- DOI
- https://doi.org/10.3389/fimmu.2019.02725
- Journal volume & issue
-
Vol. 10
Abstract
Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD).Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14−CD15high and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16hi LDGs. Clinical data on disease course, medication, and antibody status were obtained.Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group.Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD.
Keywords