کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6087406 | 1207362 | 2014 | 9 صفحه PDF | دانلود رایگان |
- Transcription factors are over-represented among MS risk factor genes.
- EOMES, TBX21, and ZMIZ1 are underexpressed in MS in 3 independent cohorts.
- Expression of EOMES, TBX21, RUNX3, TOX and CCL5 is positively correlated in blood.
- Their expression is stable over time for individuals.
- Expression of these genes in blood defines a molecular phenotype of MS.
We have identified a marked over-representation of transcription factors controlling differentiation of T, B, myeloid and NK cells among the 110 MS genes now known to be associated with multiple sclerosis (MS). To test if the expression of these genes might define molecular subtypes of MS, we interrogated their expression in blood in three independent cohorts of untreated MS (from Sydney and Adelaide) or clinically isolated syndrome (CIS, from San Francisco) patients. Expression of the transcription factors (TF) controlling T and NK cell differentiation, EOMES, TBX21 and other TFs was significantly lower in MS/CIS compared to healthy controls in all three cohorts. Expression was tightly correlated between these TFs, with other T/NK cell TFs, and to another downregulated gene, CCL5. Expression was stable over time, but did not predict disease phenotype. Optimal response to therapy might be indicated by normalization of expression of these genes in blood.
Journal: Clinical Immunology - Volume 151, Issue 1, March 2014, Pages 16-24