Association of CTLA-4 (+49 A/G) polymorphism with susceptibility to autoimmune diseases: A meta-analysis with trial sequential analysis

Yu, Lingxiang; Shao, Ming; Zhou, Tingting; Xie, Huimin; Wang, Feier; Kong, Jiangping; Xu, Shaochun; Shuai, Zongwen; Pan, Faming

doi:10.1016/j.intimp.2021.107617

Cited by 7 publications

(4 citation statements)

References 74 publications

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“…Lines of evidence showed that AS patients experienced more activated T cells, and cytotoxic T-lymphocyte antigen-4 (CTLA-4) could negatively regulate T-cell activation ( 29 ). Nonetheless, the relationship between G allele of rs231775 in CTLA-4 and AS is controversial and more studies are needed ( 30 ). Th17 cells are involved in the pathogenesis of several autoimmune diseases including AS.…”

Section: Discussionmentioning

confidence: 99%

The Associations of rs1799724 and rs361525 With the Risk of Ankylosing Spondylitis Are Dependent on HLA-B27 Status in a Chinese Han Population

Sheng

Gao

et al. 2022

Front. Immunol.

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ObjectivesHuman leucocyte antigen B27 (HLA-B27) is an important biomarker for ankylosing spondylitis (AS). However, delay in the diagnosis of AS is still common in clinical practice. Several single nucleotide polymorphisms (SNPs) in the coding gene of tumor necrosis factor alpha (TNFα) have been reported to be AS susceptibility loci. Our aim was to explore whether SNPs in TNFα could be used to improve the performance of HLA-B27 for predicting AS.MethodsFive SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) spanning TNFα were genotyped by qPCR-Invader assay in 93 AS patients and 107 healthy controls for association analysis and linkage disequilibrium (LD) analysis. Random forest algorithm was utilized to construct the predictive classifiers for AS. HLA-B was genotyped by PCR-sequence-based typing in a subset of the HLA-B27-positive subjects (38 AS patients and 5 healthy controls).ResultsThe T allele of rs1799724 was verified to significantly increase the risk of AS (OR = 4.583, p < 0.0001), while the A allele of rs361525 showed an association with the reduced AS risk (OR = 0.168, p = 0.009). In addition, the rs1799964T-rs1800630C-rs1799724T-rs1800629G-rs361525G haplotype was significantly associated with a higher risk of AS (p < 0.0001). The optimal set of variables for classifiers to predict AS only consisted of HLA-B27. Strong associations with HLA-B27 status were found in both rs1799724 (p < 0.0001) and rs361525 (p = 0.001), and all the analyzed HLA-B27-positive subjects carried HLA-B*27:04 or HLA-B*27:05.ConclusionIn the Chinese Han population, the minor allele T of rs1799724 could increase the risk of AS, while the minor allele A of rs361525 protects individuals from AS. However, the contributions of rs1799724 and rs361525 to AS risk were dependent on HLA-B27 status, suggesting the importance of taking the independence and specificity into consideration in AS susceptibility loci studies.

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Section: Discussionmentioning

confidence: 99%

The Associations of rs1799724 and rs361525 With the Risk of Ankylosing Spondylitis Are Dependent on HLA-B27 Status in a Chinese Han Population

Sheng

Gao

et al. 2022

Front. Immunol.

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“…In mouse models, the absence of CTLA-4, PD-1, BTLA, TIGIT, and VISTA results in massive lymphoproliferation, the development of autoimmune diseases, or fatal multi-organ tissue death [ 155 , 156 , 157 , 158 , 159 , 160 ]. Polymorphisms in immune checkpoint genes have been linked to the susceptibility of humans to autoimmune disorders [ 161 , 162 , 163 , 164 , 165 ].…”

Section: Implication Of Autophagy In the Commonalities Between Autoim...mentioning

confidence: 99%

Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy

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Sípos

2023

Biomedicines

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The immune system and autophagy share a functional relationship. Both innate and adaptive immune responses involve autophagy and, depending on the disease’s origin and pathophysiology, it may have a detrimental or positive role on autoimmune disorders. As a “double-edged sword” in tumors, autophagy can either facilitate or impede tumor growth. The autophagy regulatory network that influences tumor progression and treatment resistance is dependent on cell and tissue types and tumor stages. The connection between autoimmunity and carcinogenesis has not been sufficiently explored in past studies. As a crucial mechanism between the two phenomena, autophagy may play a substantial role, though the specifics remain unclear. Several autophagy modifiers have demonstrated beneficial effects in models of autoimmune disease, emphasizing their therapeutic potential as treatments for autoimmune disorders. The function of autophagy in the tumor microenvironment and immune cells is the subject of intensive study. The objective of this review is to investigate the role of autophagy in the simultaneous genesis of autoimmunity and malignancy, shedding light on both sides of the issue. We believe our work will assist in the organization of current understanding in the field and promote additional research on this urgent and crucial topic.

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“…For instance, the lack of CTLA-4, PD-1, BTLA (B-and T-lymphocyte attenuator), TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain), and VISTA (V-domain Ig suppressor of T-cell activation) was shown to cause massive lymphoproliferation, an onset of autoimmune diseases, or fatal multiorgan tissue destruction (notably CTLA-4 deficiency) (55)(56)(57)(58)(59)(60)(61). In humans, several polymorphisms of immune checkpoint genes were identified and reported to be associated with susceptibility to autoimmune diseases (62)(63)(64)(65)(66)(67)(68)(69)(70).…”

Section: Immune Checkpointsmentioning

confidence: 99%

Autoimmunity and Cancer—Two Sides of the Same Coin

et al. 2022

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Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.

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Association of CTLA-4 (+49 A/G) polymorphism with susceptibility to autoimmune diseases: A meta-analysis with trial sequential analysis

Cited by 7 publications

References 74 publications

The Associations of rs1799724 and rs361525 With the Risk of Ankylosing Spondylitis Are Dependent on HLA-B27 Status in a Chinese Han Population

The Associations of rs1799724 and rs361525 With the Risk of Ankylosing Spondylitis Are Dependent on HLA-B27 Status in a Chinese Han Population

Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy

Autoimmunity and Cancer—Two Sides of the Same Coin

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