Association of peptidylarginine deiminase IV gene expression with anti-cyclic citrullinated peptide antibody levels in rheumatoid arthritis

Abstract

Objective To explore the relationship between the gene expression of poptidylarginine deiminase Ⅳ and human leukocyte antigen (HLA)-DRBI shared epitopo (SE), anti-cycli citrullinated poptide antibody (anti-CCP), rheumatoid factor (RF) in rheumatoid arthritis (RA). Methods PADI4 expression was examined using real-time quantitative reverse transcription (RT)-PCR in 70 patients with RA, 38 patients with non-RA and 91 healthy controls. And their HLA-DRB1 *01, *04, *10 subtypes were determined by polymerase chain reaction with sequence-specific primers. Serum anti-CCP levels were measured with ELISA, serum RF levels were measured by turbidimetric immunoassay. Results The level of PADI4 expression was significantly higher in RA patients (3.43±1.97) than healthy controls (1.52±0.95, t=-8.259, P=0.000) and non-RA patients (1.41±0.79, t=-8.357, P=0.000). There was no significantly difference for PADI4 expression between anti-CCP positive and anti-CCP negative in RA (3.40±1.97, 3.78±2.15, t=0.453, P=0.688) and non-RA patients (1.34±0.93, 1.25±0.79, t=0.568 ,P=0.476). SE alleles carriers had significantly higher level of PADI4 expression than SE alleles noncarriers among RA (3.88±1.81,1.02±0.47, t=-10.382,P=0.000) and healthy controls (1.52±0.095,1.07±0.70, t=-2.457, P=0.016). PADI4 expression was higher in RF positive group than RF negative group in RA patients (t=-3.521, P=0.001), but there was no significant difference between healthy group and disease control group. There was no correlation(r=0.083, P=0.640)between the level of PADI4 expression and the content of anti-CCP in RA patients. For RA patients with anti-CCP positive, SE alleles (t=-0.690, P=0.493) and RF (t=1.330, P=0.189) did not affect serum level of anti-CCP. Conclusions PADI4 is overexpressed in RA patients. There is significant correlation between PADI4 expression and HLA-DRB1 SE alleles, and there is also certain correlation between PADI4 expression and RF. The correlation between the PADI4 expression levels and anti-CCP could not be proved in our study. Key words: Arthritis; rheumatoid; Anti-cycli citrullinated pepitide antibodies; HLA-DR antigens