Genetic association between CD96 locus and immunogenicity to anti-TNF therapy in Crohn's disease.
Pharmacogenomics J
; 19(6): 547-555, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31043678
ABSTRACT
The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn's disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e-09). This association was validated in the replication stage (P < 0.05). The risk allele for anti-TNF immunogenicity was found to be also associated with a lack of response to anti-TNF therapy (P = 0.019). These findings represent an important step toward the understanding of the immunogenicity-based mechanisms that underlie anti-TNF response in CD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
/
Antígenos CD
/
Fator de Necrose Tumoral alfa
/
Adalimumab
/
Anti-Inflamatórios
/
Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Assunto da revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha