Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Lennard Ostendorf; Ronja Mothes; Sofie van Koppen; Randall L Lindquist; Judith Bellmann-Strobl; Susanna Asseyer; Klemens Ruprecht; Tobias Alexander; Raluca A Niesner; Anja E Hauser; Friedemann Paul; Helena Radbruch

doi:10.3389/fimmu.2019.02725

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Front Immunol. 2019 Nov 29:10:2725. doi: 10.3389/fimmu.2019.02725. eCollection 2019.

Authors

Lennard Ostendorf^{1

2

3}, Ronja Mothes^{1

4}, Sofie van Koppen^{1

4}, Randall L Lindquist^{1

5}, Judith Bellmann-Strobl^{6

7}, Susanna Asseyer^{6

8

9}, Klemens Ruprecht^{7

10}, Tobias Alexander², Raluca A Niesner^{4

11}, Anja E Hauser^{2

3}, Friedemann Paul^{6

7

8

10}, Helena Radbruch¹

Affiliations

¹ Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
² 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.
³ Immunodynamics, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany.
⁴ Biophysical Analysis, Deutsches Rheuma-Forschungszentrum Berlin, A Leibniz Institute, Berlin, Germany.
⁵ Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
⁶ NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
⁷ Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
⁸ 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.
⁹ Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom.
¹⁰ Clinical 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.
¹¹ Fachbereich Veterinärmedizin, Institute of Veterinary Physiology, Freie Universität Berlin, Berlin, Germany.

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^-CD15^high and calculated their share in total PBMC leukocytes (CD45⁺) as well as the share of CD16^hi 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: autoimmunity; low-density granulocytes; multiple sclerosis; neuroinflammation; neuromyelitis optica.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Autoimmunity
Biomarkers*
Case-Control Studies
Disease Susceptibility
Female
Granulocytes / metabolism*
Humans
Immunophenotyping
Leukocyte Count
Leukocytes, Mononuclear / metabolism
Lupus Erythematosus, Systemic
Male
Middle Aged
Multiple Sclerosis / diagnosis*
Multiple Sclerosis / etiology
Multiple Sclerosis / metabolism*
Neuromyelitis Optica / diagnosis*
Neuromyelitis Optica / etiology
Neuromyelitis Optica / metabolism*

Substances

Biomarkers