Assessment of Galectin-9 in Rheumatoid Arthritis and Its Correlation With Disease Activity

NCT ID: NCT05422313

Last Updated: 2022-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

86 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-06-30

Study Completion Date

2023-12-31

Brief Summary

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Rheumatoid arthritis (RA) is an autoimmune disease in which a symmetrical Synovial inflammation, bone destruction occur in both small and big Joints. If left untreated, this illness does not generally cause death, but it does drastically affect the quality of life and life expectancy of patients. Although there is no cure for RA, patients are generally on long-term long-acting disease-modifying anti-rheumatic medications (DMARDs) to control joint inflammation, reduce joint damage, maintain joint function, and keep the illness in remission.

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

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

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

* Patients age is \> 20 years old.
* All rheumatoid arthritis patients must fulfill the 2010 ACR/EULAR criteria for RA.

Exclusion Criteria

* Patients age is \< 20 years old.
* Patient with evidence of any concomitant inflammatory disease, Acute infection or chronic inflammatory status.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Norhan mostafa Mohamed Abdelal

principle investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Sohair K Sayed, professor

Role: CONTACT

0102447771

Abeer A mokhtar, lecturer

Role: CONTACT

01008792989

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.

Reference Type BACKGROUND
PMID: 33799480 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23817958 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23408620 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30304822 (View on PubMed)

McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42. doi: 10.1038/nri2094.

Reference Type BACKGROUND
PMID: 17525752 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12079919 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30427250 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29433546 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24416634 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26435567 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20700701 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16286920 (View on PubMed)

Other Identifiers

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VDSF

Identifier Type: -

Identifier Source: org_study_id

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