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: OR(adj) = 0.93, p(adj) = 0.92; C/T: OR(adj) = 2.92, p(adj) = 0.093; T/T: OR(adj) = 15.3, p(adj) = 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-: OR(adj) = 6.20, p(adj)<0.04; SE+: OR(adj) = 0.36, p(adj) = 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.
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: OR(adj) = 0.93, p(adj) = 0.92; C/T: OR(adj) = 2.92, p(adj) = 0.093; T/T: OR(adj) = 15.3, p(adj) = 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-: OR(adj) = 6.20, p(adj)<0.04; SE+: OR(adj) = 0.36, p(adj) = 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.
Authors: T Häupl; H Appel; M Backhaus; H Burkhardt; M Grünke; A Grützkau; B Hoppe; J Listing; B Ostendorf; M Rudwaleit; J Sieper; A Skapenko; K Skriner; T Sörensen; B Stuhlmüller; A Zink; H Schulze-Koops; G-R Burmester Journal: Z Rheumatol Date: 2012-06 Impact factor: 1.372
Authors: Bo Sun; Nishant Dwivedi; Tyler J Bechtel; Janet L Paulsen; Aaron Muth; Mandar Bawadekar; Gang Li; Paul R Thompson; Miriam A Shelef; Celia A Schiffer; Eranthie Weerapana; I-Cheng Ho Journal: Sci Immunol Date: 2017-06-09
Authors: Hui-Hsin Chang; Guang-Yaw Liu; Nishant Dwivedi; Bo Sun; Yuko Okamoto; Jennifer D Kinslow; Kevin D Deane; M Kristen Demoruelle; Jill M Norris; Paul R Thompson; Jeffrey A Sparks; Deepak A Rao; Elizabeth W Karlson; Hui-Chih Hung; V Michael Holers; I-Cheng Ho Journal: JCI Insight Date: 2016-10-20
Authors: Chun Lai Too; Shahnaz Murad; Jasbir Singh Dhaliwal; Per Larsson; Xia Jiang; Bo Ding; Lars Alfredsson; Lars Klareskog; Leonid Padyukov Journal: Arthritis Res Ther Date: 2012-11-19 Impact factor: 5.156
Authors: Marian L Burr; Haris Naseem; Anne Hinks; Steve Eyre; Laura J Gibbons; John Bowes; Anthony G Wilson; James Maxwell; Ann W Morgan; Paul Emery; Sophia Steer; Lynne Hocking; David M Reid; Paul Wordsworth; Pille Harrison; Wendy Thomson; Jane Worthington; Anne Barton Journal: Ann Rheum Dis Date: 2009-05-25 Impact factor: 19.103