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Front. Immunol. | doi: 10.3389/fimmu.2019.02725

Low-Density Granulocytes are a novel immunopathological feature in both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.

 Lennard M. Ostendorf1, 2, 3*, Ronja Mothes1, 4, Sofie van Koppen1, 4,  Randall Lindquist3, 5, Judith Bellmann-Strobl6, 7,  Susanna Asseyer6, 8, 9*,  Klemens Ruprecht7, 10, Tobias Alexander2,  Raluca A. Niesner4, 11,  Anja E. Hauser2, 3,  Friedemann Paul6, 7, 8, 10 and  Helena Radbruch1
  • 1Institute for Neuropathology, Charité University Medicine Berlin, Germany
  • 2Department of Rheumatology and Clinical Immunology, Charité Medical University of Berlin, Germany
  • 3Department of Immunodynamics, German Rheumatism Research Center, Germany
  • 4Deutsches Rheuma-Forschungszentrum (DRFZ), Germany
  • 5Department of Nuclear Medicine, Charité Medical University of Berlin, Germany
  • 6NeuroCure, Charité Medical University of Berlin, Germany
  • 7Department of Neurology with Experimental Neurology, Charité Medical University of Berlin, Germany
  • 8Experimental and Clinical Research Center, Charite University Medicine Berlin, Germany
  • 9Department of Clinical Neurosciences, John Radcliffe Hospital, United Kingdom
  • 10Charité Medical University of Berlin, Germany
  • 11Department of Veterinary Medicine, Free University of Berlin, Germany

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 26 patients with NMOSD and 20 patients with MS, as well as from 18 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 analysed 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: Low-density granulocytes, Multiple Sclerosis, Neuromyelitis Optica, Neuroinflammation, Autoimmunity

Received: 02 Aug 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Ostendorf, Mothes, van Koppen, Lindquist, Bellmann-Strobl, Asseyer, Ruprecht, Alexander, Niesner, Hauser, Paul and Radbruch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Lennard M. Ostendorf, Institute for Neuropathology, Charité University Medicine Berlin, Berlin, Germany,
Dr. Susanna Asseyer, NeuroCure, Charité Medical University of Berlin, Berlin, Germany,