Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1-anchored membrane domains.
Antigen
Autoimmunity
Immunoglobulins
Multiple sclerosis
Neuroscience
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
02 10 2023
02 10 2023
Historique:
received:
16
06
2022
accepted:
01
08
2023
medline:
3
10
2023
pubmed:
10
8
2023
entrez:
10
8
2023
Statut:
epublish
Résumé
B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific recombinant monoclonal IgG1 Abs (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Abs against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients, but not in inflammatory and noninflammatory neurologic controls. CSF PLP1 complex Abs provide a pathogenic autoantibody biomarker specific for MS.
Identifiants
pubmed: 37561592
pii: 162731
doi: 10.1172/JCI162731
pmc: PMC10541191
doi:
pii:
Substances chimiques
Immunoglobulin G
0
Epitopes
0
Proteolipids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NEI NIH HHS
ID : R01 EY022936
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS025304
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS072141
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY032399
Pays : United States
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