Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis.

Hoppe, B., Häupl, T., Egerer, K., Gruber, R., Kiesewetter, H., Salama, A., Burmester, G.R. and Dörner, T. (2009): Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis. In: Annals of the Rheumatic Diseases, Vol. 68: pp. 898-903

Abstract

Background: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anticyclic 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 (SE2: 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.

• Item Type: Journal article
• Form of publication: Publisher's Version
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English