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Decreased systemic IL-7 and soluble IL-7Rα in multiple sclerosis patients.
MedLine Citation:
PMID:  22914435     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Genes and Immunity advance online publication, 23 August 2012; doi:10.1038/gene.2012.34.
Authors:
K L Kreft; E Verbraak; A F Wierenga-Wolf; M van Meurs; B A Oostra; J D Laman; R Q Hintzen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-23
Journal Detail:
Title:  Genes and immunity     Volume:  -     ISSN:  1476-5470     ISO Abbreviation:  Genes Immun.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100953417     Medline TA:  Genes Immun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands [2] Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands [3] MS Centre ErasMS, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
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