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

Abstract

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: B Hoppe, T Häupl, K Egerer, R Gruber, H Kiesewetter, A Salama, G R Burmester, T Dörner
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 68 Issue 6 Pg. 898-903 (Jun 2009) ISSN: 1468-2060 [Electronic] England
• PMID: 18633125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Antinuclear
• Autoantibodies
• Epitopes
• HLA-DR Antigens
• HLA-DRB1 Chains
• Peptides, Cyclic
• cyclic citrullinated peptide
• Rheumatoid Factor
• Hydrolases
• PADI4 protein, human
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases

Topics

• Adult
• Antibodies, Antinuclear (blood)
• Arthritis, Rheumatoid (genetics, immunology, pathology)
• Autoantibodies (blood, immunology)
• Epitopes (immunology)
• Female
• Genetic Predisposition to Disease
• Genotype
• HLA-DR Antigens (immunology)
• HLA-DRB1 Chains
• Humans
• Hydrolases (genetics)
• Joints (pathology)
• Male
• Middle Aged
• Multivariate Analysis
• Odds Ratio
• Peptides, Cyclic (immunology)
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases
• Rheumatoid Factor (analysis)