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

Journal: Neurology(R) neuroimmunology & neuroinflammation 2021;7(2):e676

PMID: 32014849

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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.

Address: 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.; 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. [email protected].

DOI: 10.1212/NXI.0000000000000676

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MeSH Terms: Adult, Autoantibodies, Biomarkers, Epitopes, Female, Humans, Immunoglobulin G, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, N-Acetylneuraminic Acid, Neuraminic Acids