BACKGROUND: Peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4 (PAD4) are two members of PAD family which are over-expressed in the multiple sclerosis (MS) brain. Through its enzymatic activity PAD2 converts myelin basic protein (MBP) arginines into citrullines - an event that may favour autoimmunity - while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling. OBJECTIVES: Our aim was to verify whether an altered epigenetic control of PAD2, as already shown in the MS brain, can be observed in peripheral blood mononuclear cells (PBMCs) of patients with MS since some of these cells also synthesize MBP. METHODS: The expression of most suitable reference genes and of PAD2 and PAD4 was assessed by qPCR. Analysis of DNA methylation was performed by bisulfite method. RESULTS: The comparison of PAD2 expression level in PBMCs from patients with MS vs. healthy donors showed that, as well as in the white matter of MS patients, the enzyme is significantly upregulated in affected subjects. Methylation pattern analysis of a CpG island located in the PAD2 promoter showed that over-expression is associated with promoter demethylation. CONCLUSION: Defective regulation of PAD2 in the periphery, without the immunological shelter of the blood-brain barrier, may contribute to the development of the autoimmune responses in MS.
BACKGROUND:Peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4 (PAD4) are two members of PAD family which are over-expressed in the multiple sclerosis (MS) brain. Through its enzymatic activity PAD2 converts myelin basic protein (MBP) arginines into citrullines - an event that may favour autoimmunity - while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling. OBJECTIVES: Our aim was to verify whether an altered epigenetic control of PAD2, as already shown in the MS brain, can be observed in peripheral blood mononuclear cells (PBMCs) of patients with MS since some of these cells also synthesize MBP. METHODS: The expression of most suitable reference genes and of PAD2 and PAD4 was assessed by qPCR. Analysis of DNA methylation was performed by bisulfite method. RESULTS: The comparison of PAD2 expression level in PBMCs from patients with MS vs. healthy donors showed that, as well as in the white matter of MS patients, the enzyme is significantly upregulated in affected subjects. Methylation pattern analysis of a CpG island located in the PAD2 promoter showed that over-expression is associated with promoter demethylation. CONCLUSION: Defective regulation of PAD2 in the periphery, without the immunological shelter of the blood-brain barrier, may contribute to the development of the autoimmune responses in MS.
Authors: Lei Yu; Robert J Dawe; Patricia A Boyle; Chris Gaiteri; Jingyun Yang; Aron S Buchman; Julie A Schneider; Konstantinos Arfanakis; Philip L De Jager; David A Bennett Journal: JAMA Neurol Date: 2017-12-01 Impact factor: 18.302
Authors: Steffan D Bos; Christian M Page; Bettina K Andreassen; Emon Elboudwarej; Marte W Gustavsen; Farren Briggs; Hong Quach; Ingvild S Leikfoss; Anja Bjølgerud; Tone Berge; Hanne F Harbo; Lisa F Barcellos Journal: PLoS One Date: 2015-03-03 Impact factor: 3.240
Authors: O G Kulakova; M R Kabilov; L V Danilova; E V Popova; O A Baturina; E Y Tsareva; N M Baulina; I S Kiselev; A N Boyko; A V Favorov; O O Favorova; V V Vlassov Journal: Acta Naturae Date: 2016 Jul-Sep Impact factor: 1.845