Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa.
Gene Ther
; 17(7): 930-7, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20376098
ABSTRACT
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen, the component of anchoring fibrils. As exogenous type VII collagen may elicit a deleterious immune response in RDEB patients during upcoming clinical trials of gene therapies or protein replacement therapies, we developed enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISPOT) assays to analyze B- and T-cell responses, to the full-length type VII collagen. The ELISA was highly sensitive and specific when tested against sera from 41 patients with epidermolysis bullosa acquisita (EBA), and the IFN-gamma ELISPOT detected a cellular response that correlated with ongoing EBA manifestations. Both tests were next applied to assess the risk of an immune response to type VII collagen in seven RDEB patients with a range of type VII collagen expression profiles. Immune responses against type VII collagen were dependent on the expression of type VII collagen protein, and consequently on the nature and position of the respective COL7A1 mutations. These immunologic tests will be helpful for the selection of RDEB patients for future clinical trials aiming at restoring type VII collagen expression, and in monitoring their immune response to type VII collagen after treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ensaio de Imunoadsorção Enzimática
/
Epidermólise Bolhosa Distrófica
/
Colágeno Tipo VII
/
Imunidade Celular
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
Limite:
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França