Assessment of Galectin-9 in Rheumatoid Arthritis and Its Correlation With Disease Activity
NCT ID: NCT05422313
Last Updated: 2022-06-22
Study Results
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Basic Information
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UNKNOWN
86 participants
OBSERVATIONAL
2022-06-30
2023-12-31
Brief Summary
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RA disease activity could be detected be DAS28 score. The DAS28 is a four-item scale that gives an absolute number reflecting disease activity. It includes the number of swollen and tender joints (SJC, TJC), the visual analogue scale of patients' assessment of their general health (VAS-GH), and the erythrocyte sedimentation rate (ESR) in the first hour.
In the pathophysiology of RA, cytokine networks play a crucial role. Rheumatoid inflammation has been linked to the generation of proinflammatory cytokines throughout time. Increased cytokine levels, such as tumour necrosis factor (TNF) and interleukin-6 (IL-6), represent rheumatoid synovial inflammation and have been linked to RA disease activity and anti-cytokine therapeutic response. The relationship between circulating cytokine levels and the phenotype of RA illness is, however, poorly understood.
Anti-citrullinated peptide antibodies (ACPA) are effective in the diagnosis of RA and have been linked to joint destruction progression and therapy response in RA patients. However, the relationship between ACPA status and proinflammatory cytokines during the course of RA illness is yet unknown.
Galectins are lectins with carbohydrate recognition domains (CRDs) that are extremely similar in sequence and exclusively bind to β--galactoside carbs. There are at least 15 galectins found in mammals, each having one or two CRDs comprising roughly 130 amino acids. Galectins have a wide range of activities due to their ubiquitous distribution, including mRNA splicing, programmed cell death, cell cycle control, activation, adhesion, migration, and cell differentiation.
Galectin-9 (Gal-9) is abundantly present in lymph nodes, bone marrow, liver, thymus, and spleen. It is expressed by immune cells, endothelial cells, and fibroblasts and plays an important role in regulating inflammation and immune reactions. Gal-9 is a ligand for T cell immunoglobulin and mucin-containing-moleculte-3 (Tim-3) that is expressed on CD4+ T helper (Th) 1 and Th17 and sends inhibitory signals to Tim-3. As a result of its interaction with Tim-3, Gal-9 suppresses pro-inflammatory T cell responses, and the Gal-9/Tim-3 pathway causes apoptosis of CD4+ Th1 or Th17 cells.
Considering that RA is a Th1-polarized autoimmune illness, dysregulated Gal-9 levels may induce an innate/adaptive immunity imbalance, resulting in pathological rheumatoid inflammation. Gal-9 has been demonstrated to mediate angiogenesis and inflammatory cell infiltration in inflammatory arthritis.
These findings show that Gal-9 may have a role in the inflammatory processes of rheumatoid arthritis. As a result, we concentrated on Gal-9 and postulated that it could be involved in the pathogenesis of RA. The levels of serum Gal-9 in individuals with RA were studied in this study, and the results were compared to clinical indicators
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Detailed Description
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Conditions
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Study Design
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CASE_CONTROL
RETROSPECTIVE
Study Groups
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56 patients with RA.
Patients age is \> 20 years old.
No interventions assigned to this group
: 30 age-matched Healthy
Individual must be without a prior history of chronic inflammation or any form of arthritis. - .
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* All rheumatoid arthritis patients must fulfill the 2010 ACR/EULAR criteria for RA.
Exclusion Criteria
* Patient with evidence of any concomitant inflammatory disease, Acute infection or chronic inflammatory status.
ALL
No
Sponsors
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Assiut University
OTHER
Responsible Party
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Norhan mostafa Mohamed Abdelal
principle investigator
Central Contacts
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References
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Floudas A, Canavan M, McGarry T, Mullan R, Nagpal S, Veale DJ, Fearon U. ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis. Cells. 2021 Mar 14;10(3):647. doi: 10.3390/cells10030647.
Gieseke F, Kruchen A, Tzaribachev N, Bentzien F, Dominici M, Muller I. Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation. Eur J Immunol. 2013 Oct;43(10):2741-9. doi: 10.1002/eji.201343335. Epub 2013 Jul 23.
Golden-Mason L, McMahan RH, Strong M, Reisdorph R, Mahaffey S, Palmer BE, Cheng L, Kulesza C, Hirashima M, Niki T, Rosen HR. Galectin-9 functionally impairs natural killer cells in humans and mice. J Virol. 2013 May;87(9):4835-45. doi: 10.1128/JVI.01085-12. Epub 2013 Feb 13.
Yap HY, Tee SZ, Wong MM, Chow SK, Peh SC, Teow SY. Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development. Cells. 2018 Oct 9;7(10):161. doi: 10.3390/cells7100161.
McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42. doi: 10.1038/nri2094.
Naranjo A, Ojeda S, Francisco F, Erausquin C, Rua-Figueroa I, Rodriguez-Lozano C. Fibromyalgia in patients with rheumatoid arthritis is associated with higher scores of disability. Ann Rheum Dis. 2002 Jul;61(7):660-1. doi: 10.1136/ard.61.7.660. No abstract available.
Ogata A, Kato Y, Higa S, Yoshizaki K. IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review. Mod Rheumatol. 2019 Mar;29(2):258-267. doi: 10.1080/14397595.2018.1546357. Epub 2019 Jan 3.
O'Brien MJ, Shu Q, Stinson WA, Tsou PS, Ruth JH, Isozaki T, Campbell PL, Ohara RA, Koch AE, Fox DA, Amin MA. A unique role for galectin-9 in angiogenesis and inflammatory arthritis. Arthritis Res Ther. 2018 Feb 12;20(1):31. doi: 10.1186/s13075-018-1519-x.
Li S, Yu Y, Koehn CD, Zhang Z, Su K. Galectins in the Pathogenesis of Rheumatoid Arthritis. J Clin Cell Immunol. 2013 Sep 30;4(5):1000164. doi: 10.4172/2155-9899.1000164.
Xia T, Zheng XF, Qian BH, Fang H, Wang JJ, Zhang LL, Pang YF, Zhang J, Wei XQ, Xia ZF, Zhao DB. Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines. Dis Markers. 2015;2015:795043. doi: 10.1155/2015/795043. Epub 2015 Sep 6.
Zhu C, Anderson AC, Kuchroo VK. TIM-3 and its regulatory role in immune responses. Curr Top Microbiol Immunol. 2011;350:1-15. doi: 10.1007/82_2010_84.
Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005 Dec;6(12):1245-52. doi: 10.1038/ni1271. Epub 2005 Nov 13.
Other Identifiers
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VDSF
Identifier Type: -
Identifier Source: org_study_id
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