Xenogeneic Neu5Gc and self-glycan Neu5Ac epitopes are potential immune targets in MS

Kayluz F Boligan; Johanna Oechtering; Christian W Keller; Benjamin Peschke; Robert Rieben; Nicolai Bovin; Ludwig Kappos; Richard D Cummings; Jens Kuhle; Stephan von Gunten; Jan D Lünemann

doi:10.1212/NXI.0000000000000676

Xenogeneic Neu5Gc and self-glycan Neu5Ac epitopes are potential immune targets in MS

Neurol Neuroimmunol Neuroinflamm. 2020 Feb 3;7(2):e676. doi: 10.1212/NXI.0000000000000676. Print 2020 Mar.

Affiliations

¹ From the Institute of Pharmacology (K.F.B., S.v.G.), University of Bern, Switzerland; Neurologic Clinic and Policlinic (J.O., L.K., J.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Switzerland; Department of Neurology with Institute of Translational Neurology (C.W.K., J.D.L.), University Hospital Münster, University of Münster, Germany; Laboratory of Neuroinflammation (C.W.K., B.P., J.D.L.), Institute of Experimental Immunology, University of Zurich, Switzerland; Department for BioMedical Research (DBMR) (R.R.), University of Bern, Switzerland; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science (N.B.), Moscow, Russia; Auckland University of Technology (N.B.), New Zealand; and Department of Surgery (R.D.C.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
² From the Institute of Pharmacology (K.F.B., S.v.G.), University of Bern, Switzerland; Neurologic Clinic and Policlinic (J.O., L.K., J.K.), Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Switzerland; Department of Neurology with Institute of Translational Neurology (C.W.K., J.D.L.), University Hospital Münster, University of Münster, Germany; Laboratory of Neuroinflammation (C.W.K., B.P., J.D.L.), Institute of Experimental Immunology, University of Zurich, Switzerland; Department for BioMedical Research (DBMR) (R.R.), University of Bern, Switzerland; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Science (N.B.), Moscow, Russia; Auckland University of Technology (N.B.), New Zealand; and Department of Surgery (R.D.C.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. jan.luenemann@ukmuenster.de.

Abstract

Objective: To explore the repertoire of glycan-specific immunoglobulin G (IgG) antibodies in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: A systems-level approach combined with glycan array technologies was used to determine specificities and binding reactivities of glycan-specific IgGs in treatment-naive patients with RRMS compared with patients with noninflammatory and other inflammatory neurologic diseases.

Results: We identified a unique signature of glycan-binding IgG in MS with high reactivities to the dietary xenoglycan N-glycolylneuraminic acid (Neu5Gc) and the self-glycan N-acetylneuraminic acid (Neu5Ac). Increased reactivities of serum IgG toward Neu5Gc and Neu5Ac were additionally observed in an independent, treatment-naive cohort of patients with RRMS.

Conclusion: Patients with MS show increased IgG reactivities to structurally related xenogeneic and human neuraminic acids. The discovery of these glycan-specific epitopes as immune targets and potential biomarkers in MS merits further investigation.

MeSH terms

Adult
Autoantibodies / blood
Autoantibodies / cerebrospinal fluid
Autoantibodies / metabolism*
Biomarkers
Epitopes
Female
Humans
Immunoglobulin G / blood
Immunoglobulin G / cerebrospinal fluid
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / diagnosis
Multiple Sclerosis, Relapsing-Remitting / immunology*
Multiple Sclerosis, Relapsing-Remitting / metabolism*
N-Acetylneuraminic Acid / immunology*
Neuraminic Acids / immunology*

Substances

Autoantibodies
Biomarkers
Epitopes
Immunoglobulin G
Neuraminic Acids
N-glycolylneuraminic acid
N-Acetylneuraminic Acid