title: The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls.
abstract: BACKGROUND
  The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have been confirmed to encode different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially with regard to autoimmune diseases.
  
  
  METHODS
  We have investigated the mRNA expression of known PTPN22 splice forms with TaqMan real-time PCR in relation to ZNF592 as an endogenous reference in peripheral blood cells from three independent cohorts with RA patients (n = 139) and controls (n = 111) of Caucasian origin. Polymorphisms in the PTPN22 locus (25 SNPs) and phenotypic data (gender, disease activity, ACPA and RF status) were used for analysis. Additionally, we addressed possible effects of methotrexate treatment on PTPN22 expression.
  
  
  RESULTS
  We found consistent differences in the expression of the PTPN22 splice forms in unstimulated peripheral blood mononuclear cells between RA patients and normal controls. This difference was more pronounced when comparing the ratio of splice forms and was not affected by methotrexate treatment.
  
  
  CONCLUSIONS
  Our data show that RA patients and healthy controls have a shift in balance of expression of splice forms derived from the PTPN22 gene. This balance seems not to be caused by treatment and may be of importance during immune response due to great structural differences in the encoded PTPN22 proteins.
authors.affiliation: Department of Medicine, Rheumatology Unit, CMM L8:04, Karolinska Institutet & Karolinska Universitetssjukhuset, Stockholm, S-17176, Sweden. marcus.ronninger@ki.se.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ronninger
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Guo
authors.forename: Klementy
authors.initials: K
authors.lastname: Shchetynsky
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Padmalatha S
authors.initials: PS
authors.lastname: Reddy
authors.forename: Maria
authors.initials: M
authors.lastname: Seddighzadeh
authors.forename: James D
authors.initials: JD
authors.lastname: Clark
authors.forename: Lih-Ling
authors.initials: LL
authors.lastname: Lin
authors.forename: Margot
authors.initials: M
authors.lastname: O'Toole
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov