Galectin-9 as a biomarker for disease activity in systemic lupus erythematosus

Matsuoka, Naoki; Fujita, Yuya; Temmoku, Jumpei; Furuya, Makiko Yashiro; Asano, Tomohiko; Sato, Shuzo; Matsumoto, Haruki; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Kozuru, Hideko; Yastuhashi, Hiroshi; Migita, Kiyoshi

doi:10.1371/journal.pone.0227069

Cited by 52 publications

(46 citation statements)

References 38 publications

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“…We previously demonstrated that circulating Gal-9 is elevated and partly correlated with the titers of autoantibodies in patients with autoimmune diseases [28,29]. However, the more elevated levels of serum galectin-9 were demonstrated and positively correlated with disease activity in an autoinflammatory disease, ASD.…”

Section: Discussionmentioning

confidence: 98%

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

et al. 2020

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Background: The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin, and mucincontaining-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still's disease (ASD). Methods: Serum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with the clinical features of ASD. Results: Serum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41-39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57-10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58-5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p < 0.001, sTIM-3; r = 0.78, p < 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p < 0.001, sTIM-3; r = 0.71, p < 0.001) and ASD disease activity score (Pouchot's score, Gal-9; r = 0.66, p < 0.001, sTIM-3; r = 0.59, p < 0.001), whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores. Conclusions: Serum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecules may be implicated in the autoinflammatory process seen in ASD.

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Section: Discussionmentioning

confidence: 98%

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

et al. 2020

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“…Overexpression of galectin-9 in islets could prolong grafts survival in NOD/SCID mice, suggesting galectin-9 may be released from pancreatic β -cells to terminate TH1-mediated inflammation [ 28 ]. Many evidences demonstrated that galactin-9 was a novel, easy to measure biomarker for type 1 IFN signatures [ 29 ]. In our study, plasma galectin-9 levels in patients with obesity comorbid type 2 diabetes significantly increased and positively correlated with weight, BMI, hipline, UA, and especially islet-related indicators insulin and C-peptides.…”

Section: Discussionmentioning

confidence: 99%

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

Sun

Zou

Ding

et al. 2020

Journal of Diabetes Research

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Aims. Obesity is highly associated with type 2 diabetes mellitus (T2DM). The TIM3/galectin-9 pathway plays an important role in immune tolerance. Herein, we aimed to investigate the expression of TIM3 and galectin-9 in peripheral blood and to evaluate their clinical significance in patients with obesity and obesity-related T2DM. Methods. We performed flow cytometry on peripheral blood samples from healthy donors (HC), patients with simple obesity (OB), and patients with obesity comorbid T2DM (OD). The expression of TIM3 on CD3+, CD4+, and CD8+ T cells was determined. The level of galectin-9 in plasma was detected by ELISA. Results. We demonstrated the enhancement of TIM3 on CD3+, CD4+, and CD8+ T cells in the OB group when compared with healthy controls, while it was decreased significantly in the OD group. The TIM3+CD8+ T cells of the OB group were positively correlated with risk factors including BMI, body fat rate, and hipline. The concentration of galectin-9 of the OD group in plasma was significantly higher than that of healthy donors and the OB group. Moreover, the level of galectin-9 of the OD group was positively correlated with fasting insulin and C-peptide, which were two clinical features that represented pancreatic islet function in T2DM. Conclusions. Our results suggested that TIM3 and galectin-9 may be potential biomarkers related to the pathogenesis of obesity-related T2DM.

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“…Galectin-9, which was first identified as a potent eosinophil chemoattractant, is currently known as a versatile immunomodulator ( 26 , 27 ). Notably, up-regulated levels of gal-9 were reported in inflammatory bowel disease ( 27 ) and systemic lupus erythematosus ( 28 , 29 ). The role of gal-9 in immunoregulation seems to be complicated.…”

Section: Galectin-9 As An Immune Regulatormentioning

confidence: 99%

Galectin-9: A Suppressor of Atherosclerosis?

Zhu

et al. 2020

Front. Immunol.

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It is no longer controversial that atherosclerosis is a vascular wall chronic inflammatory disease mediated by cells of innate and adaptive immunity. Galectin-9 (Gal-9) seems to be a crucial regulator of T-cell immunity by inducing apoptosis in specific T-cell subpopulations associated with autoimmunity and inflammatory disease. Accumulating evidence showed that galectin-9 signaling via T-cell immunoglobulin mucin 3 (TIM-3) is concerned with different regulatory functions in autoimmunity, including direct depletion of pro-inflammatory T-cells, expanding the number of regulatory T cells, altering macrophages to an anti-inflammatory state and the induction of repressive myeloidderived suppressor cells. In addition, anti-Tim-3-Ab administration increased atherosclerotic plaque formation by blocking Tim-3-galectin-9 interaction. Hence, we hypothesize that galectin-9 may be a novel therapy for atherosclerotic disease. Further researches are needed to investigate the precise effect of galectin-9 in the process of atherosclerosis.

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Galectin-9 as a biomarker for disease activity in systemic lupus erythematosus

Cited by 52 publications

References 38 publications

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

Elevated serum levels of checkpoint molecules in patients with adult Still’s disease

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

Galectin-9: A Suppressor of Atherosclerosis?

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