Research

The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls

Marcus Ronninger^*†, Yongjing Guo^†, Klementy Shchetynsky, Andrew Hill, Mohsen Khademi, Tomas Olsson, Padmalatha S Reddy, Maria Seddighzadeh, James D Clark, Lih-Ling Lin, Margot O'Toole and Leonid Padyukov

• * Corresponding author: Marcus Ronninger marcus.ronninger@ki.se

• † Equal contributors

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Genome Medicine 2012, 4:2 doi:10.1186/gm301

Published: 20 January 2012

Abstract (provisional)

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 confirmed different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially in the aspect of 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.