Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
13 10 2022
13 10 2022
Historique:
received:
22
04
2022
revised:
20
09
2022
accepted:
22
09
2022
entrez:
13
10
2022
pubmed:
14
10
2022
medline:
18
10
2022
Statut:
epublish
Résumé
Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood-brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.
Identifiants
pubmed: 36229064
pii: 5/12/e202201496
doi: 10.26508/lsa.202201496
pmc: PMC9559755
pii:
doi:
Substances chimiques
Autoantibodies
0
Autoantigens
0
Guanosine
12133JR80S
RNA
63231-63-0
Adenosine
K72T3FS567
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 : NINDS NIH HHS
ID : R01 NS046769
Pays : United States
Organisme : CIHR
ID : MOP-159703
Pays : Canada
Informations de copyright
© 2022 Muslimov et al.
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