Decreased systemic IL-7 and soluble IL-7R alpha in multiple sclerosis patients

Polymorphisms (single-nucleotide polymorphism (SNP)) in the interleukin-7 receptor-alpha (IL-7R alpha)/IL-7 pathway are associated with an increased risk to develop multiple sclerosis (MS). The rs6897932 SNP in the IL-7R alpha leads to increased soluble IL-7R alpha production. Given the functional interaction between sIL-7R alpha, membrane-bound IL-7R alpha and IL-7, we assessed IL-7, mIL-7R alpha and sIL-7R alpha levels in MS patients and healthy controls (HCs). One-hundred and twenty eight MS patients had significantly lower sIL-7R alpha levels compared with 73 HCs. The levels of sIL-7R alpha increased dose-dependent upon rs6897932 [C] risk allele carriership in both HCs and MS. Next, we hypothesized that lower sIL-7R alpha could result in a higher mIL-7R alpha to soluble IL-7R alpha ratio. Indeed, 52 MS patients had significantly increased mIL-7R alpha to sIL-7R alpha 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-7R alpha 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-7R alpha ratio. The soluble IL-7R alpha levels correlate with the rs6897932 [C] risk allele carriership. The skew at the IL-7 and IL-7R alpha level may influence responsiveness of IL-7R alpha(+) cells.