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Clinical Rheumatology

, Volume 35, Issue 5, pp 1181–1188 | Cite as

Prevalence of soluble peptidylarginine deiminase 4 (PAD4) and anti-PAD4 antibodies in autoimmune diseases

  • Naoto Umeda
  • Isao Matsumoto
  • Hoshimi Kawaguchi
  • Yuko Kurashima
  • Yuya Kondo
  • Hiroto Tsuboi
  • Hiroshi Ogishima
  • Takeshi Suzuki
  • Yayoi Kagami
  • Takuya Sakyu
  • Akihito Ishigami
  • Naoki Maruyama
  • Takayuki Sumida
Original Article

Abstract

The objectives of this study are to investigate the prevalence of PAD4 and anti-PAD4 antibodies (Abs) in autoimmune diseases and to clarify their association with anticitrullinated protein antibodies (ACPAs) and shared epitope (SE) in patients with rheumatoid arthritis (RA). Levels of human PAD4 and anti-PAD4 Abs in serum or plasma were measured using sandwich ELISA. Samples were obtained from patients with RA (n = 148), SLE (n = 36), or SS (n = 37) and from healthy controls (HCs; n = 40). Antibodies against cyclic citrullinated glucose-6-phosphate isomerase (GPI) (CCG)-2, CCG-7, anti-CEP-1, and anti-CCP Abs were also measured using ELISA. Patients with RA were genotyped for HLA-DRB1. The human PAD4 and anti-PAD4 Ab levels were compared with the ACPA and SE in patients with RA. The PAD4 levels were 111.9 U/ml in the RA, 30.4 U/ml in the SLE, 81.9 U/ml in the SS patients, and 46.6 U/ml in the HCs. The PAD4 levels were significantly higher in the RA than in the SLE patients or the HCs. Anti-PAD4 Abs were detected in 29.7 % of the patients with RA, but not in the patients with SLE or SS, nor in the HCs. In the RA patients, the PAD4 levels in the anti-PAD4 Ab-negative group were significantly higher than those in the anti-PAD4 Ab-positive group. Moreover, anti-CCG-2, CCG-7, CEP-1, and anti-CCP Ab levels were significantly higher in the anti-PAD4 Ab-positive group than in the anti-PAD4 Ab-negative group. In the RA patients, the PAD4 levels were not correlated with ACPAs. Neither PAD4 nor anti-PAD4 Abs were significantly correlated with the presence of SE alleles. The PAD4 levels were higher in RA than in SLE or HC. Anti-PAD4 Abs appeared specifically in patients with RA. Moreover, anti-PAD4 Abs were associated with ACPAs.

Keywords

Anticitrullinated protein antibodies Anti-peptidylarginine deiminase 4 antibodies Peptidylarginine deiminase 4 Rheumatoid arthritis Shared epitope 

Notes

Acknowledgments

We thank Naoyuki Tsuchiya for support with HLA-DR genotyping.

Disclosures

None

Supplementary material

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Supplementary Fig. 1 (DOC 21kb)
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Supplementary Fig. 2 (DOC 21kb)
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Supplementary Fig. 3 (DOC 22kb)
10067_2015_3082_MOESM4_ESM.doc (28 kb)
Supplementary Table 1 (DOC 28kb)

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2015

Authors and Affiliations

  • Naoto Umeda
    • 1
  • Isao Matsumoto
    • 1
  • Hoshimi Kawaguchi
    • 1
  • Yuko Kurashima
    • 1
  • Yuya Kondo
    • 1
  • Hiroto Tsuboi
    • 1
  • Hiroshi Ogishima
    • 1
  • Takeshi Suzuki
    • 1
  • Yayoi Kagami
    • 2
  • Takuya Sakyu
    • 3
  • Akihito Ishigami
    • 2
  • Naoki Maruyama
    • 2
  • Takayuki Sumida
    • 1
  1. 1.Department of Internal Medicine, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Molecular Regulation of AgingTokyo Metropolitan Institute of GerontologyTokyoJapan
  3. 3.Biotechnology Research GroupFujirebioTokyoJapan

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