Specific overexpression of TNFAIP9 in CD14+CD16- monocytes in patients with rheumatoid arthritis- Comparative analysis with TNFAIP3-
Chinatsu Takai1, 2, Isao Matsumoto1, Asuka Inoue1, Naoto Umeda1, Yuki Tanaka1, Yuko Kurashima1, Yoko Wada2, Ichiei Narita2, Takayuki Sumida1
1
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine,
University of Tsukuba, Tsukuba, Japan 2
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate
School of Medicine and Dental Sciences, Niigata, Japan
Corresponding author: Isao Matsumoto, MD, PhD Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan Tel/Fax: +81-29-853-3186 e-mail:
[email protected] Running title: TNFAIP9 and TNFAIP3 in RA Keywords: rheumatoid arthritis, TNFα-induced proteins, TNFAIP9, monocytes, pathogenesis
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1111/cei.12606 This article is protected by copyright. All rights reserved.
Clinical Experimental Immunology TNFAIP9 and TNFAIP3 in RA. Page 2
Abstract Objective: The TNFα-induced proteins TNFAIP9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). Methods: TNFAIP9 and TNFAIP3 mRNA expression was determined in peripheral blood mononuclear cells (PBMC) of RA patients and healthy subjects (control). Flow cytometry was used to analyze the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14+ cells stimulated with TNFα and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. Results: TNFAIP9 expression was significantly higher while TNFAIP3 expression was lower in PBMC of RA (n=36) than the control (n=24) (p