[Peptidyl arginine deiminase 4 participates in the pathogenesis of rheumatoid arthritis by influencing histone methylation].

OBJECTIVE

To explore the probable function of peptidyl arginine deiminase 4 (PAD4) in rheumatoid arthritis(RA).

METHODS

Real-time quantitative polymerase chain reaction (PCR) was used to determine the expression of PAD4 mRNA in peripheral blood mononucleated cells (PBMCs) from 60 RA patients and 40 healthy individuals. Asymmetric di-methylation of histone H3R17, symmetric di-methylation and mono-methylation of H4R3 were semi-quantified by Western blotting in 12 patients with osteoarthritis (OA), 26 patients with RA and 10 healthy controls.

RESULTS

PAD4 mRNA in RA was significantly higher than that in healthy controls[34.6(16.7, 70.8) vs 20.6(11.1, 51.8), P < 0.05]. The level of histone H3R17 asymmetric di-methylation in RA was significantly higher than that of OA or control groups (71.34 ± 25.65 vs 37.18 ± 18.62 vs 50.67 ± 13.99, P < 0.01) , which was positively related to Tender joint count and Swollen joint count in 28 joints (r = 0.418, P = 0.034;r = 0.402, P = 0.042). The level of histone H4R3 symmetric di-methylation was similar in RA,OA and control groups (75.02 ± 20.35 vs 57.92 ± 22.77 vs 68.37 ± 17.57, P > 0.05) . The level of histone H4R3 mono-methylation in RA patients was significantly lower than that of OA patients and healthy individuals (11.24 ± 7.81 vs 32.77 ± 30.77 vs 51.20 ± 47.14, P < 0.05). The level of histone H4R3 mono-methylation in RA patients was negatively correlated to PAD4 (r = -0.643, P < 0.01) . The level of histone H3R17 asymmetric di-methylation and H4R3 symmetric di-methylation was not associated with PAD4 level in RA group (r = -0.185, P = 0.377; r = 0.198, P = 0.344).

CONCLUSIONS

The level of histone H3R17 asymmetric di-methylation is significantly higher and the level of histone H4R3 mono-methylation is significantly lower in RA patients comparing with OA and control groups. Abnormality of histone methylation may be one of the mechanisms for the development of RA. PAD4 probably plays an important role in rheumatoid arthritis by influencing histone methylation.