PT - JOURNAL ARTICLE AU - B Hoppe AU - T Häupl AU - K Egerer AU - R Gruber AU - H Kiesewetter AU - A Salama AU - G R Burmester AU - T Dörner TI - Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis AID - 10.1136/ard.2008.091983 DP - 2009 Jun 01 TA - Annals of the Rheumatic Diseases PG - 898--903 VI - 68 IP - 6 4099 - http://ard.bmj.com/content/68/6/898.short 4100 - http://ard.bmj.com/content/68/6/898.full SO - Ann Rheum Dis2009 Jun 01; 68 AB - Background: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anti-cyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA.Objectives: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed.Methods: 373 patients with RA were studied. SE, padi4_94C>T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score.Results: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C>T genotype (C/C: ORadj = 0.93, padj = 0.92; C/T: ORadj = 2.92, padj = 0.093; T/T: ORadj = 15.3, padj = 0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C>T with ANAs was observed, with noteworthy differences depending on SE status (SE−: ORadj = 6.20, padj<0.04; SE+: ORadj = 0.36, padj = 0.02) and significant heterogeneity between the two SE strata (p = 0.006).Conclusions: PADI4 genotype in combination with anti-CCPs and SE modulates clinical and serological characteristics of RA.