Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, PADI4 Polymorphisms, and Clinical Characteristics in Rheumatoid Arthritis

Kari Guderud; Marthe Thoresen Mæhlen; Gry Beate Namløs Nordang; Marte Kathrine Viken; Bettina Kulle Andreassen; Øyvind Molberg; Siri Tennebø Flåm; Benedicte Alexandra Lie

doi:10.3899/jrheum.170769

Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, PADI4 Polymorphisms, and Clinical Characteristics in Rheumatoid Arthritis

J Rheumatol. 2018 Aug;45(9):1211-1219. doi: 10.3899/jrheum.170769. Epub 2018 Jun 1.

Authors

Kari Guderud^{1

2}, Marthe Thoresen Mæhlen^{1

2}, Gry Beate Namløs Nordang^{1

2}, Marte Kathrine Viken^{1

2}, Bettina Kulle Andreassen^{1

2}, Øyvind Molberg^{1

2}, Siri Tennebø Flåm^{1

2}, Benedicte Alexandra Lie^{3

4}

Affiliations

¹ From the Department of Medical Genetics, and the Department of Immunology, University of Oslo and Oslo University Hospital; K.G. Jebsen Inflammation Research Centre, University of Oslo; Department of Rheumatology, Oslo University Hospital; Department of Rheumatology, Diakonhjemmet Hospital; Department of Research, Cancer Registry of Norway, Institute for Population-based Research, Oslo, Norway.
² K. Guderud, M Pharm, Department of Medical Genetics, and the K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital; M.T. Mæhlen, PhD, Department of Medical Genetics, University of Oslo and Oslo University Hospital, and Department of Rheumatology, Diakonhjemmet Hospital; G.B. Nordang, PhD, Department of Medical Genetics, University of Oslo and Oslo University Hospital; M.K. Viken, PhD, Department of Medical Genetics, and Department of Immunology, University of Oslo and Oslo University Hospital, and K.G. Jebsen Inflammation Research Centre; B.K. Andreassen, PhD, Department of Research, Cancer Registry of Norway, Institute for Population-Based Research; Ø. Molberg, PhD, Department of Rheumatology, Oslo University Hospital; S.T. Flåm, BS, Department of Medical Genetics, and the K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital; B.A. Lie, PhD, Department of Medical Genetics, and Department of Immunology, University of Oslo and Oslo University Hospital, and K.G. Jebsen Inflammation Research Centre.
³ From the Department of Medical Genetics, and the Department of Immunology, University of Oslo and Oslo University Hospital; K.G. Jebsen Inflammation Research Centre, University of Oslo; Department of Rheumatology, Oslo University Hospital; Department of Rheumatology, Diakonhjemmet Hospital; Department of Research, Cancer Registry of Norway, Institute for Population-based Research, Oslo, Norway. b.a.lie@medisin.uio.no.
⁴ K. Guderud, M Pharm, Department of Medical Genetics, and the K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital; M.T. Mæhlen, PhD, Department of Medical Genetics, University of Oslo and Oslo University Hospital, and Department of Rheumatology, Diakonhjemmet Hospital; G.B. Nordang, PhD, Department of Medical Genetics, University of Oslo and Oslo University Hospital; M.K. Viken, PhD, Department of Medical Genetics, and Department of Immunology, University of Oslo and Oslo University Hospital, and K.G. Jebsen Inflammation Research Centre; B.K. Andreassen, PhD, Department of Research, Cancer Registry of Norway, Institute for Population-Based Research; Ø. Molberg, PhD, Department of Rheumatology, Oslo University Hospital; S.T. Flåm, BS, Department of Medical Genetics, and the K.G. Jebsen Inflammation Research Centre, University of Oslo and Oslo University Hospital; B.A. Lie, PhD, Department of Medical Genetics, and Department of Immunology, University of Oslo and Oslo University Hospital, and K.G. Jebsen Inflammation Research Centre. b.a.lie@medisin.uio.no.

PMID: 29858238
DOI: 10.3899/jrheum.170769

Abstract

Objective: We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the PADI4 gene together with clinical variables in rheumatoid arthritis (RA).

Methods: Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 available from previous studies). Genotyping of PADI4 was performed using TaqMan assays in 945 patients and 1118 controls. Clinical data, anticitrullinated protein antibodies (ACPA) status, shared epitope status, and a combined genetic risk score were also available.

Results: Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also ACPA-positive. No association was observed between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status.

Conclusion: Taken together, the results from these combined serological, genetic, and clinical analyses suggest that anti-PAD4 appears to be a bystander autoantibody with no current clinical utility in RA.

Keywords: ANTI-PAD4; ANTICITRULLINATED PROTEIN ANTIBODIES; AUTOANTIBODIES; PADI4; RHEUMATOID ARTHRITIS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Arthritis, Rheumatoid / blood
Arthritis, Rheumatoid / genetics*
Arthritis, Rheumatoid / immunology
Autoantibodies*
Epitopes
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminases / genetics*
Protein-Arginine Deiminases / immunology

Substances

Autoantibodies
Epitopes
PADI4 protein, human
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminases