Human C5-specific single-chain variable fragment ameliorates brain injury in a model of NMOSD.
Neurol Neuroimmunol Neuroinflamm
; 6(3): e561, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-31044149
Objective: Using phage display, we sought to screen single-chain variable fragments (scFvs) against complement C5 to treat neuromyelitis optica spectrum disorder (NMOSD). Methods: After 5 rounds of phage display, we isolated individual clones and identified phage clones specifically binding to C5 using ELISA. Using aquaporin-4 (AQP4)-transfected cells in vitro, we confirmed whether these scFvs prevented complement-dependent cytotoxicity (CDC) caused by the serum of patients with NMOSD and human complement (hC). We selected an NMOSD mouse model, in which intracerebral NMOSD immunoglobulin G (IgG) and hC injections induce NMOSD-like lesions in vivo. Results: We obtained scFvs to test specificity and blocking efficiency. The scFv C5B3 neutralized C5 in the complement activation pathway, which prevented AQP4-IgG-mediated CDC in AQP4-transfected cells. In an NMOSD mouse model, C5B3 prevented AQP4 and astrocyte loss, decreased demyelination, and reduced inflammatory infiltration and membrane attack complex formation in lesions. Conclusions: We used phage display to screen C5B3 against C5, which was effective in inhibiting cytotoxicity in vitro and preventing CNS pathology in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
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Complemento C5
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Neuromielite Óptica
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Ativação do Complemento
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Aquaporina 4
/
Anticorpos de Cadeia Única
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Neurol Neuroimmunol Neuroinflamm
Ano de publicação:
2019
Tipo de documento:
Article
País de publicação:
Estados Unidos