Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.
Nat Immunol
; 22(2): 128-139, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33398182
ABSTRACT
Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enteropatias Perdedoras de Proteínas
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Complemento C5
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Ativação do Complemento
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Metabolismo Energético
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Inativadores do Complemento
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Anticorpos Monoclonais Humanizados
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Hipoproteinemia
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Imunidade Inata
Tipo de estudo:
Observational_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Turquia