In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 11 ( 2021-11-18), p. e0260254-
Abstract:
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. Methods 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. Results 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. Conclusions 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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0260254
DOI:
10.1371/journal.pone.0260254.g001
DOI:
10.1371/journal.pone.0260254.g002
DOI:
10.1371/journal.pone.0260254.g003
DOI:
10.1371/journal.pone.0260254.g004
DOI:
10.1371/journal.pone.0260254.g005
DOI:
10.1371/journal.pone.0260254.g006
DOI:
10.1371/journal.pone.0260254.t001
DOI:
10.1371/journal.pone.0260254.t002
DOI:
10.1371/journal.pone.0260254.s001
DOI:
10.1371/journal.pone.0260254.s002
DOI:
10.1371/journal.pone.0260254.s003
DOI:
10.1371/journal.pone.0260254.s004
DOI:
10.1371/journal.pone.0260254.s005
DOI:
10.1371/journal.pone.0260254.s006
DOI:
10.1371/journal.pone.0260254.r001
DOI:
10.1371/journal.pone.0260254.r002
DOI:
10.1371/journal.pone.0260254.r003
DOI:
10.1371/journal.pone.0260254.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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