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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05422313
• Other study ID #: VDSF
• Status: Not yet recruiting
• Start date: June 2022
• Est. completion date: December 2023

Study information

• Verified date: June 2022
• Source: Assiut University
• Contact: Sohair K Sayed, professor
• Phone: 0102447771
• Email: Ksoher3[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 86
• Est. completion date: December 2023
• Est. primary completion date: November 2023
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (12)

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). pii: 647. doi: 10.3390/cells10030647. — View Citation

Gieseke F, Kruchen A, Tzaribachev N, Bentzien F, Dominici M, Müller 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. — View Citation

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. — View Citation

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). pii: 1000164. — View Citation

McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42. Review. — View Citation

Naranjo A, Ojeda S, Francisco F, Erausquin C, Rúa-Figueroa I, Rodríguez-Lozano C. Fibromyalgia in patients with rheumatoid arthritis is associated with higher scores of disability. Ann Rheum Dis. 2002 Jul;61(7):660-1. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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). pii: E161. doi: 10.3390/cells7100161. Review. — View Citation

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. Review. — View Citation

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. Epub 2005 Nov 13. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To correlate galectin-9 level with RA disease activity.	use galectin-9 to determine disease activity	1.5 years