Association between T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Genetic Polymorphisms and Susceptibility to Autoimmune Diseases

Zhang, Rui; Li, He; Bai, Linfu; Duan, Jun

doi:10.1080/08820139.2019.1599009

Cited by 13 publications

(5 citation statements)

References 45 publications

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“…However, it is thought that abnormal activation of both innate and adaptive immune systems, particularly the IL-23/IL-17 axis and Th1/Th2/Th17 effector T-cell lineage, plays a key role (9)(10)(11)(12). A meta-analysis of Chinese populations revealed that TIM-3 polymorphisms are significantly associated with an increased risk of autoimmune diseases, such as rheumatoid arthritis, Graves' disease, multiple sclerosis, systemic lupus erythematosus, AS, CD, and UC (13). Our previous study identified a temporary increase in TIM-3 expression levels in a mouse model of anterior chamberassociated immune deviation (ACAID) (14).…”

Section: Introductionmentioning

confidence: 97%

Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis

et al. 2023

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BackgroundWe aimed to investigate the causal association between TIM-3, an immune checkpoint inhibitor, and anterior uveitis (AU), as well as associated systemic immune diseases.Materials and methodsWe performed two-sample Mendelian randomization (MR) analyses to estimate the causal effects of TIM-3 on AU and three associated systemic diseases, namely ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) associated with AU, AS, CD, and UC were selected as the outcomes: AU GWAS with 2,752 patients with acute AU accompanied with AS (cases) and 3,836 AS patients (controls), AS GWAS with 968 cases and 336,191 controls, CD GWAS with 1,032 cases and 336,127 controls, and UC GWAS with 2,439 cases and 460,494 controls. The TIM-3 dataset was used as the exposure (n = 31,684). Four MR methods, namely, inverse-variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode, were used in this study. Comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the potential impact of horizontal pleiotropy.ResultsOur studies show that TIM-3 is significantly associated with CD using the IVW method (OR = 1.001, 95% CI = 1.0002–1.0018, P-value = 0.011). We also found that TIM-3 may be a protective factor for AU although these results lacked significance (OR = 0.889, 95% CI = 0.631–1.252, P-value = 0.5). No association was observed between the genetic predisposition to particular TIM-3 and susceptibility to AS or UC in this study. No potential heterogeneities or directional pleiotropies were observed in our analyses.ConclusionAccording to our study, a small correlation was observed between TIM-3 expression and CD susceptibility. Additional studies in different ethnic backgrounds will be necessary to further explore the potential roles and mechanisms of TIM-3 in CD.

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Section: Introductionmentioning

confidence: 97%

Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis

et al. 2023

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“…Autoimmune diseases are caused by a combination of genetic factors and environmental factors (Luppi et al, 1995). In particular, the role of genetic factors has been confirmed by a number of studies (Gabrielsen et al, 2016;Zhong et al, 2018;Zhang et al, 2019). Hundreds of risk susceptibility genes related to AIDs have been identified through genome-wide scans and large-scale single-nucleotide polymorphism (SNP) association studies (Lessard et al, 2012;Kochi, 2016).…”

Section: Introductionmentioning

confidence: 99%

Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis

Liang

2021

Front. Genet.

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The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.

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“…Treatment with an antagonistic antibody against TIM1 showed beneficial effects in experimental colitis models. Moreover, knocking out TIM3 exacerbated colitis severity in vivo and led to increased pITK levels in vitro in LPMCs 1 2 3 4 5 6 7 8 .…”

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confidence: 99%

Unraveling the Intricacies of IBD: Insights into TIM1 and TIM3 Surface Proteins and their Intracellular Signaling Pathways in View of a Possible Treatment

Knauss,

Gabel,

Neurath

et al. 2024

Zeitschrift Für Gastroenterologie

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Association between T-Cell Immunoglobulin and Mucin Domain 3 (TIM-3) Genetic Polymorphisms and Susceptibility to Autoimmune Diseases

Cited by 13 publications

References 45 publications

Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis

Association of TIM-3 with anterior uveitis and associated systemic immune diseases: a Mendelian randomization analysis

Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis

Unraveling the Intricacies of IBD: Insights into TIM1 and TIM3 Surface Proteins and their Intracellular Signaling Pathways in View of a Possible Treatment

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