SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

Lennard Ostendorf,Raluca A Niesner,Friedemann Paul,Ankelien Duchow,Helena Radbruch,Victoria Stiglbauer,Robert Biesen,Dominik Seelow,Philipp Dittert,Klemens Ruprecht,Anja E Hauser,Werner Stenzel,Judith Bellmann-Strobl

doi:10.1038/s41598-021-89786-0

Abstract

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was—apart from those patients receiving interferon treatment—not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

Highlights

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases
We investigated the SIGLEC1 expression on C D14+ monocytes in the peripheral blood of MS and NMOSD patients as well as in healthy controls
We identified SIGLEC1+ on CD68+ HLA-DR+ myeloid cells in active inflammatory MS lesions and a range of other inflammatory, infectious or malignant brain lesions

Summary

Introduction

We aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases. SIGLEC1 expression on monocytes was—apart from those patients receiving interferon treatment—not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. Multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) are both chronic, demyelinating inflammatory diseases of the central nervous system that are a significant cause of disability in the young. Freie Universität Berlin, Humboldt‐Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, Berlin Institute of Health, Berlin, Germany. Corporate Member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.

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