| Objective: To detect the levels of PAD4mRNA and histone arginine methylation levelsin histone H3R17/H4R3in peripheral blood mononuclear cells with rheumatoid arthritis(RA) and study the association between PAD4and histone arginine methylation levelsin histone H3R17asymmetric di-methylation and H4R3symmetric di-methylation andmono-methylation in RA，as well as anti-CCP antibodies,DAS28score, ESR, RF, CRP,disease duration. And explore its value in the pathogenesis of RA.Methods:60patients with RA,40healthy individual, were included in thestudy．Peripheral blood mononuclear cells (PBMCs) derived from10ml of whole bloodwere separated by gradient centrifugation, and total RNA of PBMCs was extracted andtranscripted into cDNA.Real-time quantitative PCR was used to determine theexpression of PAD4mRNA in peripheral blood mononuclear cells(PBMCs),and therelationship between PAD4and their clinical indexes were analyzed.Simultaneously, thehistone H3R17asymmetric di-methylation and H4R3symmetric di-methylation andmono-methylation was semi-quantified by Western blotting from12osteoarthritis (OA)and selected26patients with RA and10healthy individual．SPSS software13.0wasused for statistical analysis.Values were expressed as mean±SD for normallydistributed variables and median with interquartile range (IQR) for non-normallydistributed data.Two groups were compared using independent samples t-test, among the three groups using analysis of variance (ANOVA). Bivariate correlations wereassessed using Pearson’s and Spearman’s correlation coefficients for normally andnon-normally distributed data, respectively.Results:1)The level of PAD4mRNA of RA was significantly higher than healthycontrols([34.6(16.7,70.8)] vs20.6(11.1,51.8)],P<0.05). The PADI4level was positivelyrelated to anti-CCP antibodies(r=0.527，P<0.001),DAS28score (r=0.416，P=0.001),ESR (r=0.371,P=0.004)， RF,(r=0.287,P=0.030) and was not associated with CRPlevels (r=0.015,p=0.919), disease duration (r=0.064,p=0.625)．2) The level of histone H3R17asymmetric di-methylation in RA was significantlyhigher than OA and healthy individua（l71.34±25.65vs37.18±18.62vs50.67±13.99,P﹤0.05）. The level of histone H3R17asymmetric di-methylation was not associatedwith PAD4in RA (r=-0.185, p=0.377),but was positively related toTJC andSTJ(r=0.418,p=0,034;r=0.402,p=0.042).3) The level of histone H4R3symmetric di-methylation in RA was also higher than OAand healthy individual,（75.02±20.35vs57.92±22.77vs68.37±17.57, P﹥0.05）,butthe difference was not statistically significant.The level of histone H4R3symmetricdi-methylation was not associated with PAD4in RA(r=0.198, p=0.344).4) The level of histone H4R3mono-methylation in RA was significantly lower thanOA and healthy individual (11.24±7.81vs32.77±30.77vs51.20±47.14, P﹤0.05). Butthe level of histone H4R3mono-methylation in RA was negative related to PAD4（r=-0.643，P＜0.001）,however was not associated with anti-CCP, antibody, DAS28score, ESR, CRP, RF, Disease duration, Joint function classification,TJC,SJC,HAQscore，Duration of morning stiffness,X-ray stage(r=-0.147，p=0.505；r=0.037，p=0.860；r=-0.091， p=0.664；r=0.078， p=0.725；r=-0.212，p=0.309；r=0.162，p=0.440；r=0.276，p=0.172；r=0.275，p=0.174；r=0.243，p=0.232；r=0.272，p=0.179；r=0.335， p=0.095；r=0.285，p=0.304).Conclusion：1)The expression of PAD4mRNA in RA is higher than controls and was positivelyrelated to anti-CCP antibodies,DAS28score, ESR,RF, which may play an important rolein the pathogenesis of RA．2)The level of histone H3R17asymmetric di-methylation was significantly higher andthe level of histone H4R3mono-methylation was significantly lower in RA than OA andhealthy individual，abnormal of histone methylation may be one of the reasons for thepathogenesis of RA.3） The level of histone H3R17asymmetric di-methylation and H4R3symmetricdi-methylation was not associated with PAD4， the level of histone H4R3mono-methylation was negative related to PAD4in RA，PAD4probably play animportent role in rheumatoid arthritis by influncing histone H3R17/H4R3methylation. |
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