Haplotypes of the interleukin 7 receptor alpha gene are correlated with altered expression in whole blood cells in multiple sclerosis.
IL7 regulates T cell survival, differentiation and proliferation. The alpha chain of its receptor, CD127, is polymorphic, and its haplotypes are associated with recovery from transplantation and with the autoimmune disease multiple sclerosis (MS), especially primary progressive MS (PPMS). We demonstrate that two CD127 haplotypes are highly associated with the proportion of the mRNA encoding the soluble isoform of CD127 (P<or=0.001). The soluble isoform is over-represented (P<or=0.002) in PPMS peripheral blood, irrespective of haplotype, and the MS susceptibility haplotype produces more of the soluble isoform. CD127 mRNA is underexpressed (P<or=0.001) in PPMS. Neutrophils, which produce very low levels of CD127 mRNA, were over-represented in our PPMS cohort (P<0.02). CD127 expression is lower in more differentiated cells, such as Th1s, which can be elevated in MS. A higher proportion of these two abundant cell types in peripheral blood could be the basis for the observed reduction in CD127 mRNA. CD127 expression may be a biomarker for these potentially pathologically significant leukocyte types. These significant haplotypic effects on expression are likely to modulate regulation, differentiation and function of T cell subsets in health and disease.
McKay
F C
FC
Westmead Millennium Institute, University of Sydney, Sydney, Australia.
Swain
L I
LI
Schibeci
S D
SD
Rubio
J P
JP
Kilpatrick
T J
TJ
Heard
R N
RN
Stewart
G J
GJ
Booth
D R
DR
D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D013223:Statistics as Topic; D018417:Th1 Cells / Q000378:metabolism*
D012333:RNA, Messenger; D020395:Receptors, Interleukin-7