title: Methylation-dependent PAD2 upregulation in multiple sclerosis peripheral blood.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Cellular Biotechnologies and Haematology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.
authors: Roberta
authors: R
authors: Calabrese
authors: Michele
authors: M
authors: Zampieri
authors: Rosella
authors: R
authors: Mechelli
authors: Viviana
authors: V
authors: Annibali
authors: Tiziana
authors: T
authors: Guastafierro
authors: Fabio
authors: F
authors: Ciccarone
authors: Giulia
authors: G
authors: Coarelli
authors: Renato
authors: R
authors: Umeton
authors: Marco
authors: M
authors: Salvetti
authors: Paola
authors: P
authors: Caiafa
mesh_terms: D000328:Adult; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000235:genetics*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases; D015854:Up-Regulation
chemical_list: D004676:Myelin Basic Protein; D006867:Hydrolases; C000620352:PADI2 protein, human; D000080064:Protein-Arginine Deiminase Type 2; D000076342:Protein-Arginine Deiminases