Nucleic acid sensing receptors in systemic lupus erythematosus: development of novel DNA- and/or RNA-like analogues for treating lupus

Lenert, Petar

doi:10.1111/j.1365-2249.2010.04176.x

Cited by 29 publications

(28 citation statements)

References 182 publications

(234 reference statements)

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“…IFN plays an important role in SLE pathogenesis by enhancing autoimmune processes and disease complications (Lenert, 2010). Studies on IFN-induced genes improve our understanding of the regulatory mechanisms involved in activity and development of SLE.…”

Section: Discussionmentioning

confidence: 99%

Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis

Silva¹,

Lima²,

Addobbati³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Systemic lupus erythematosus (SLE) is a complex autoimmune disorder presenting heterogeneous clinical manifestations.A number of genes involved in SLE susceptibility are related to the type I interferon (IFN) pathway. IFN mediates innate immune responses and its increased levels contribute to the breakdown of peripheral tolerance. Interferon-induced helicase C domain 1 (IFIH1) activates and modulates IFN responses through its caspase recruitment domain. In this study, we analyzed four IFIH1 single nucleotide polymorphisms (SNPs): rs6432714, rs10930046, rs1990760, and rs3747517, in 337 patients with SLE and 373 healthy individuals from southeast and northeast Brazil. Our results did not find an association between IFIH1 SNPs and SLE (P value >0.025 after Bonferroni's adjustment). However, metaanalysis of peer-reviewed articles from 2008 to 2015 and data from this study indicated an association between rs1990760 and SLE onset (P < 0.05). This is the first association analysis on IFIH1 polymorphisms and SLE susceptibility in Brazilian populations.

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Section: Discussionmentioning

confidence: 99%

Association of interferon-induced helicase C domain (IFIH1) gene polymorphisms with systemic lupus erythematosus and a relevant updated meta-analysis

Silva¹,

Lima²,

Addobbati³

et al. 2016

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…While there are multiple TLRs, there are two that are of particular interest: TLR-7 that recognizes single stranded viral RNA and TLR-9 that recognizes bacterial hypomethylated DNA. 112 These two TLRs are implicated in both the activation of B cells in murine models and SLE patients, as well as in the generation of type I IFN, which can in turn also upregulate B cells. 112 TLR-9 recognizes hypomethylated CpG-oligodeoxynucleotides (CpG-ODN), a motif present in bacterial DNA which has been found to induce T cell independent activation of B cells as well as the activation of other APCs such as dendritic cells.…”

Section: Tlr Inhibitorsmentioning

confidence: 99%

“…112 These two TLRs are implicated in both the activation of B cells in murine models and SLE patients, as well as in the generation of type I IFN, which can in turn also upregulate B cells. 112 TLR-9 recognizes hypomethylated CpG-oligodeoxynucleotides (CpG-ODN), a motif present in bacterial DNA which has been found to induce T cell independent activation of B cells as well as the activation of other APCs such as dendritic cells. 113 Humans recognize foreign DNA as foreign because it is not methylated as is human DNA.…”

Section: Tlr Inhibitorsmentioning

confidence: 99%

“…SLE patients though have abnormalities in DNA methylation leading to segments of hypomethylated DNA. 112 Theoretically, when SLE patients release apoptotic bodies and create immune complexes with chromatin, they are exposing this hypomethylated DNA to TLR-9. 112 This has been shown in vitro where immune complexes containing DNA and IgG were bound to autoreactive B cells and induced the activation of the cell through TLR-9.…”

Section: Tlr Inhibitorsmentioning

confidence: 99%

“…112 Theoretically, when SLE patients release apoptotic bodies and create immune complexes with chromatin, they are exposing this hypomethylated DNA to TLR-9. 112 This has been shown in vitro where immune complexes containing DNA and IgG were bound to autoreactive B cells and induced the activation of the cell through TLR-9. 114 Administration of CpG-ODN in several murine models of SLE is associated with worse disease activity.…”

Section: Tlr Inhibitorsmentioning

confidence: 99%

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