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GDP-l-fucose synthase is a CD4 + T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Planas Raquel, Santos Radleigh, Tomas-Ojer Paula, Cruciani Carolina, Lutterotti Andreas, Faigle Wolfgang, Schaeren-Wiemers Nicole, Espejo Carmen, Eixarch Herena, Pinilla Clemencia, Martin Roland, Sospedra Mireia,
Project Suche nach Kandidaten-Autoantigenen und viralen/bakteriellen Triggern der Multiplen Sklerose
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Original article (peer-reviewed)

Journal Science Translational Medicine
Volume (Issue) 10(462)
Page(s) eaat4301 - eaat4301
Title of proceedings Science Translational Medicine
DOI 10.1126/scitranslmed.aat4301

Abstract

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood. By using a brain-infiltrating CD4 + T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)– l -fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4 + T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP- l -fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide. These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.
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