Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

Yao, Liqiong; Liu, Bei; Jiang, Li; Zhou, Lei; Liu, Xiaoju

doi:10.1080/10245332.2018.1530179

Cited by 12 publications

(14 citation statements)

References 25 publications

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“…The subjects with thrombocytopenia caused by organ diseases (such as lesion of liver, kidney, or spleen), drugs, chemoradiotherapy, or HIV were excluded in this research. The inclusion criteria in this study were not only limited to the low platelet counts (< 100 × 10 9 /L) without underlying disease, also known as primary ITP 30 , but also the patients suffered from thrombocytopenia triggered by autoimmune diseases were also accepted.…”

Section: Discussionmentioning

confidence: 99%

“…The previous ITP-related studies only suggested that CTLA4 gene polymorphism may affect the severity of chronic thrombocytopenia 37 , or SNPs of CTLA4 were related to the mRNA transcription level. In Yao’s study, they showed that patients with primary ITP had a lower expression level of CTLA4 in Chinese Han children (5.43 ± 3.21 years old) when compared to controls, but the rs11571315 was not susceptible to primary ITP 30 . However, our data demonstrated that rs11571315 was a susceptible SNP for primary ITP in the Taiwan population.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study

Chen

Lin

Wen

et al. 2022

Sci Rep

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Thrombocytopenia is a condition where the platelet count is under 100 × 109/L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymorphisms (SNPs) of genes related to T cell activation. There were 32 ITP patients and 30 healthy controls enrolled in this study. PCR and sequencing were used to find out the significant SNPs, which we focused on the promoter region of CTLA4 and CD28. In this study, the ITP cases were divided into primary ITP group, secondary ITP group, and the combination of the two to the follow-up analysis. Moreover, dual-luciferase reporter assay was used to evaluate the transcription activity of the significant SNP. We found the − 1765_rs11571315 of CTLA4 gene was associated with primary ITP (p = 0.006), secondary ITP (p = 0.008), and the combination of the two (p = 0.003). Moreover, the −318_rs5742909 also had statistical significance in secondary ITP group that was only caused by autoimmune disease (p = 0.019). In functional study, the rs5742909 would decrease 19% of the transcription activity when it carried a T-allele at this position (p = 0.040). It was noted that CTLA4 gene polymorphism was related to ITP but not CD28. According to our results, we surmised that CTLA4 is involved in the pathogenesis of ITP, and the secondary ITP result from the lower CTLA4 expression that leads to T cell over-activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study

Chen

Lin

Wen

et al. 2022

Sci Rep

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“…In the Egyptian population, the T-G haplotype of the CD40 gene SNP rs1883832 is associated with an increased risk of ITP development ( 55 ), which also suggested that the immune checkpoint pathway may be involved in the pathogenesis and development of ITP. In addition, a case-control association analysis of 277 Chinese children revealed that abnormal expression, instead of genetic polymorphisms of CTLA4, may be correlated with susceptibility to ITP ( 56 ). Here, we found that mRNA and protein levels of CD28 in the CT genotype were higher than those in TT genotype in T cells of ITP patients, suggesting that heterozygotes of CD28 rs1980422 play an important role in increased expression of CD28 in ITP.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint-Related Gene Polymorphisms Are Associated With Primary Immune Thrombocytopenia

et al. 2021

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Cancer immunotherapy by immune checkpoint blockade has been effective in the treatment of certain tumors. However, the association between immune checkpoints and autoimmune diseases remains elusive and requires urgent investigation. Primary immune thrombocytopenia (ITP), characterized by reduced platelet count and a consequent increased risk of bleeding, is an autoimmune disorder with a hyper-activated T cell response. Here, we investigated the contribution of immune checkpoint-related single-nucleotide polymorphisms (SNPs), including CD28, ICOS, PD1, TNFSF4, DNAM1, TIM3, CTLA4, and LAG3 to the susceptibility and therapeutic effects of ITP. In this case-control study, 307 ITP patients and 295 age-matched healthy participants were recruited. We used the MassARRAY system for genotyping immune checkpoint-related SNPs. Our results revealed that rs1980422 in CD28 was associated with an increased risk of ITP after false discovery rate correction (codominant, CT vs. TT, OR = 1.788, 95% CI = 1.178–2.713, p = 0.006). In addition, CD28 expression at both the mRNA and protein levels was significantly higher in patients with CT than in those with the TT genotype (p = 0.028 and p = 0.001, respectively). Furthermore, the T allele of PD1 rs36084323 was a risk factor for ITP severity and the T allele of DNAM1 rs763361 for corticosteroid-resistance. In contrast, the T allele of LAG3 rs870849 was a protective factor for ITP severity, and the T allele of ICOS rs6726035 was protective against corticosteroid-resistance. The TT/CT genotypes of PD1 rs36084323 also showed an 8.889-fold increase in the risk of developing refractory ITP. This study indicates that immune checkpoint-related SNPs, especially CD28 rs1980422, may be genetic factors associated with the development and treatment of ITP patients. Our results shed new light on prognosis prediction, disease severity, and discovering new therapeutic targets.

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“…In Table 5, we summarized several studies for clinical conditions of significant CTLA4 SNPs in this study. These SNPs were associated with immune-related diseases or conditions, including Grave’s disease [29], organ or stem cell transplantation [30,31], susceptibility of cancer [32,33,34], and thrombocytopenia [35]. CTLA4 participates in immune regulation and genetic variations in CTLA4 gene would influence immune response and then alter the risk of suffering from a disease [36].…”

Section: Discussionmentioning

confidence: 99%

Association of CTLA4 Gene Polymorphism with Transfusion Reaction after Infusion of Leukoreduced Blood Component

Wen

Lin

Wang

et al. 2019

JCM

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Leukocytes and cytokines in blood units have been known to be involved in febrile non-hemolytic transfusion reaction (FNHTR), and these adverse reactions still occur while using pre-storage leukoreduced blood products. Blood transfusion is similar to transplantation because both implant allogeneic cells or organs into the recipient. CTLA4 gene polymorphism was found to be associated with graft-versus-host disease in hematopoietic stem cell transplantation. We performed a prospective cohort study at a major tertiary care center to investigate the correlation of CTLA4 gene polymorphism and transfusion reactions. Selected CTLA4 gene SNPs were genotyped and compared between patients with transfusion-associated adverse reactions (TAARs) and healthy controls. Nineteen patients and 20 healthy subjects were enrolled. There were 4 SNPs showing differences in allele frequency between patients and controls, and the frequency of “A” allele of rs4553808, “G” allele of rs62182595, “G” allele of rs16840252, and “C” allele of rs5742909 were significantly higher in patients than in controls. Moreover, these alleles also showed significantly higher risk of TAARs (OR = 2.357, 95%CI: 1.584–3.508, p = 0.02; OR = 2.357, 95%CI: 1.584–3.508, p = 0.02; OR = 2.462, 95%CI: 1.619–3.742, p = 0.008; OR = 2.357, 95%CI: 1.584–3.508, p = 0.02; OR = 2.357, 95%CI: 1.584–3.508, p = 0.02, respectively). The present study demonstrated the correlation of CTLA4 gene polymorphism and transfusion reaction, and alleles of 4 CTLA4 SNPs with an increased risk of TAARs were found. It is important to explore the potential immune regulatory mechanism affected by SNPs of costimulatory molecules, and it could predict transfusion reaction occurrence and guide preventive actions.

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Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

Cited by 12 publications

References 25 publications

Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study

Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study

Immune Checkpoint-Related Gene Polymorphisms Are Associated With Primary Immune Thrombocytopenia

Association of CTLA4 Gene Polymorphism with Transfusion Reaction after Infusion of Leukoreduced Blood Component

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