Decreased systemic IL-7 and soluble IL-7Rα in multiple sclerosis patients.
Genes Immun
; 13(7): 587-92, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22914435
ABSTRACT
Polymorphisms (single-nucleotide polymorphism (SNP)) in the interleukin-7 receptor-α (IL-7Rα)/IL-7 pathway are associated with an increased risk to develop multiple sclerosis (MS). The rs6897932 SNP in the IL-7Rα leads to increased soluble IL-7Rα production. Given the functional interaction between sIL-7Rα, membrane-bound IL-7Rα and IL-7, we assessed IL-7, mIL-7Rα and sIL-7Rα levels in MS patients and healthy controls (HCs). One-hundred and twenty eight MS patients had significantly lower sIL-7Rα levels compared with 73 HCs. The levels of sIL-7Rα increased dose-dependent upon rs6897932 [C] risk allele carriership in both HCs and MS. Next, we hypothesized that lower sIL-7Rα could result in a higher mIL-7Rα to soluble IL-7Rα ratio. Indeed, 52 MS patients had significantly increased mIL-7Rα to sIL-7Rα ratio for both CD4 and CD8 T cells compared with 44 HCs. Given the supposed role of IL-7 in autoimmunity, we determined whether sIL-7Rα influences IL-7 levels. IL-7 levels were significantly decreased in 40 MS patients compared with 40 HCs. In conclusion, MS patients had lower free IL-7 and a higher membrane to soluble IL-7Rα ratio. The soluble IL-7Rα levels correlate with the rs6897932 [C] risk allele carriership. The skew at the IL-7 and IL-7Rα level may influence responsiveness of IL-7Rα(+) cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-7
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Receptores de Interleucina-7
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Esclerose Múltipla
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Genes Immun
Ano de publicação:
2012
Tipo de documento:
Article