Hoppe, B.; Häupl, T.; Egerer, K.; Gruber, R.; Kiesewetter, H.; Salama, A.; Burmester, G.R.; Dörner, T.
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
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
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