Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

<h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling....

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Autores principales:	Haruki Matsumoto, Yuya Fujita, Tomoyuki Asano, Naoki Matsuoka, Jumpei Temmoku, Shuzo Sato, Makiko Yashiro–Furuya, Kohei Yokose, Shuhei Yoshida, Eiji Suzuki, Toru Yago, Hiroshi Watanabe, Atsushi Kawakami, Kiyoshi Migita
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5146651f887140efad76d4db9c829101
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spelling	oai:doaj.org-article:5146651f887140efad76d4db9c8291012021-11-25T06:19:40ZAssociation between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis1932-6203https://doaj.org/article/5146651f887140efad76d4db9c8291012021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601500/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. <h4>Methods</h4> Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. <h4>Results</h4> Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. <h4>Conclusions</h4> Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.Haruki MatsumotoYuya FujitaTomoyuki AsanoNaoki MatsuokaJumpei TemmokuShuzo SatoMakiko Yashiro–FuruyaKohei YokoseShuhei YoshidaEiji SuzukiToru YagoHiroshi WatanabeAtsushi KawakamiKiyoshi MigitaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
description	<h4>Background</h4> Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. <h4>Methods</h4> Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. <h4>Results</h4> Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. <h4>Conclusions</h4> Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.
format	article
author	Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita
author_facet	Haruki Matsumoto Yuya Fujita Tomoyuki Asano Naoki Matsuoka Jumpei Temmoku Shuzo Sato Makiko Yashiro–Furuya Kohei Yokose Shuhei Yoshida Eiji Suzuki Toru Yago Hiroshi Watanabe Atsushi Kawakami Kiyoshi Migita
author_sort	Haruki Matsumoto
title	Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
title_short	Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
title_full	Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
title_fullStr	Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
title_full_unstemmed	Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
title_sort	association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5146651f887140efad76d4db9c829101
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Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

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