The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis

GRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, including blood, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a...

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Main Authors: Guoyin Liu, Jianping Wu, Yongqiang Wang, Yuansheng Xu, Chun Xu, Guilin Fang, Xin Li, Jianmin Chen
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Bioengineering
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Online Access:https://www.mdpi.com/2306-5354/12/1/58
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author Guoyin Liu
Jianping Wu
Yongqiang Wang
Yuansheng Xu
Chun Xu
Guilin Fang
Xin Li
Jianmin Chen
author_facet Guoyin Liu
Jianping Wu
Yongqiang Wang
Yuansheng Xu
Chun Xu
Guilin Fang
Xin Li
Jianmin Chen
author_sort Guoyin Liu
collection DOAJ
description GRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, including blood, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a scarcity of data linking both intracellular and extracellular GRP78/Bip to disease activity and progression of RA. This study was undertaken to investigate the differential expression of GRP78/Bip in blood, SF, and synovium, and to determine their association with disease activity and progression of RA. Patients with RA, osteoarthritis (OA), and traumatic meniscal injury (TMI) without radiographic OA were consecutively recruited for the study. Among patients with RA, six different subgroups were established based on their disease activity and progression. Disease activity was measured using the DAS28 (Disease activity scores in 28 joints) criterion, while disease progression was evaluated using the Steinbrocker classification grade. The levels of GRP78/Bip, TNF-α, and IL-10 were significantly elevated in the serum, SF, and synovium of patients with RA when compared to both the control (CON, TMI Patients) and the inflammation control (iCON, OA Patients) groups (<i>p</i> < 0.05). In terms of disease activity status, as opposed to remission status in RA, the levels of GRP78/Bip, TNF-α, and IL-10 were all elevated in serum and synovium (<i>p</i> < 0.05). However, GRP78/Bip and IL-10 levels were found to be reduced in SF, while TNF-α levels remained elevated. With respect to disease progression in RA, GRP78/Bip levels exhibited a positive correlation with both the stage of RA and the levels of TNF-α and IL-10 in serum and synovium. Nonetheless, a negative correlation was observed between GRP78/Bip levels and the stage of RA in SF, while positive correlations with the levels of TNF-α and IL-10 persisted. The differential expression of GRP78/Bip in blood, SF, and synovium indicated that the potential role and function of GRP78/Bip might vary depending on its specific location within these biological fluids and tissues. The presence of intracellular and extracellular GRP78/Bip was associated with disease activity and progression of RA, suggesting the involvement of GRP78/Bip in the pathogenesis and development of this debilitating autoimmune disorder, as well as its potential as a biomarker for monitoring disease activity and progression of RA.
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spelling doaj-art-0b4fc569a9d34e6eb75cea7ad116e5182025-01-24T13:23:07ZengMDPI AGBioengineering2306-53542025-01-011215810.3390/bioengineering12010058The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid ArthritisGuoyin Liu0Jianping Wu1Yongqiang Wang2Yuansheng Xu3Chun Xu4Guilin Fang5Xin Li6Jianmin Chen7Department of Orthopedics, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaDepartment of Obstetrics, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaDepartment of Rehabilitation, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaDepartment of Orthopedics, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaDepartment of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, ChinaDepartment of Rheumatology, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaDepartment of Orthopedics, Central Military Commission Joint Logistics Support Force 904th Hospital, Wuxi 214044, ChinaDepartment of Orthopedics, The Affiliated Jinling Hospital of Nanjing Medical University, Nanjing 211166, ChinaGRP78/BiP, a stress-induced protein and autoantigen in rheumatoid arthritis (RA), exhibits different expressions in various biological fluids and tissues, including blood, synovial fluid (SF), and synovium, all of which are pertinent to the disease activity and progression of RA; however, there is a scarcity of data linking both intracellular and extracellular GRP78/Bip to disease activity and progression of RA. This study was undertaken to investigate the differential expression of GRP78/Bip in blood, SF, and synovium, and to determine their association with disease activity and progression of RA. Patients with RA, osteoarthritis (OA), and traumatic meniscal injury (TMI) without radiographic OA were consecutively recruited for the study. Among patients with RA, six different subgroups were established based on their disease activity and progression. Disease activity was measured using the DAS28 (Disease activity scores in 28 joints) criterion, while disease progression was evaluated using the Steinbrocker classification grade. The levels of GRP78/Bip, TNF-α, and IL-10 were significantly elevated in the serum, SF, and synovium of patients with RA when compared to both the control (CON, TMI Patients) and the inflammation control (iCON, OA Patients) groups (<i>p</i> < 0.05). In terms of disease activity status, as opposed to remission status in RA, the levels of GRP78/Bip, TNF-α, and IL-10 were all elevated in serum and synovium (<i>p</i> < 0.05). However, GRP78/Bip and IL-10 levels were found to be reduced in SF, while TNF-α levels remained elevated. With respect to disease progression in RA, GRP78/Bip levels exhibited a positive correlation with both the stage of RA and the levels of TNF-α and IL-10 in serum and synovium. Nonetheless, a negative correlation was observed between GRP78/Bip levels and the stage of RA in SF, while positive correlations with the levels of TNF-α and IL-10 persisted. The differential expression of GRP78/Bip in blood, SF, and synovium indicated that the potential role and function of GRP78/Bip might vary depending on its specific location within these biological fluids and tissues. The presence of intracellular and extracellular GRP78/Bip was associated with disease activity and progression of RA, suggesting the involvement of GRP78/Bip in the pathogenesis and development of this debilitating autoimmune disorder, as well as its potential as a biomarker for monitoring disease activity and progression of RA.https://www.mdpi.com/2306-5354/12/1/58intracellular GRP78/BiPextracellular GRP78/BiPrheumatoid arthritis (RA)disease activitydisease progression
spellingShingle Guoyin Liu
Jianping Wu
Yongqiang Wang
Yuansheng Xu
Chun Xu
Guilin Fang
Xin Li
Jianmin Chen
The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
Bioengineering
intracellular GRP78/BiP
extracellular GRP78/BiP
rheumatoid arthritis (RA)
disease activity
disease progression
title The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
title_full The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
title_fullStr The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
title_full_unstemmed The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
title_short The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis
title_sort differential expressions and associations of intracellular and extracellular grp78 bip with disease activity and progression in rheumatoid arthritis
topic intracellular GRP78/BiP
extracellular GRP78/BiP
rheumatoid arthritis (RA)
disease activity
disease progression
url https://www.mdpi.com/2306-5354/12/1/58
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