Consideration of IL-2, IFN-γ and IL-4 expression and methylation levels in CD4+ T cells as a predictor of rejection in kidney transplant

Soyöz, Mustafa; Pehlivan, Melek; Tatar, Erhan; Çerçi, Burcu; Çöven, Hatice İlayhan Karahan; Ayna, Tülay Kılıçaslan

doi:10.1016/j.trim.2021.101414

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…Another study reported that HTLV-1 causes atherosclerosis by inducing inflammation [15]. Emerging research indicates that dysregulation of immune-inflammatory pathways, including IL-4 and TNF, play a significant role in the pathogenesis of various diseases, such as panic disorder and kidney transplant rejection [16][17][18]. There is a lack of existing data regarding immune-inflammatory pathway methylation in individuals with ST-segment elevation myocardial infarction (STEMI).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic biomarkers for ST-segment elevation myocardial infarction using RNA methylation regulators

Li,

Ma,

Zhao

et al. 2024

Egypt J Med Hum Genet

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Aims Additional evidence has indicated a correlation between N6-methyladenosine (m6A) RNA methylation and cardiovascular disease. Nevertheless, the alterations in RNA methylation modification and the expression of numerous genes remains unclear. This study aimed to identify the role of m6A in ST-segment elevation myocardial infarction (STEMI). Methods Two microarray datasets (GSE123342 and GSE59867) were downloaded from the GEO database. After merging the data and batch normalization, differentially expressed regulators were identified using the limma package. Subtyping consistency analysis was performed to group samples. The random forest algorithm and support vector machine were used to identify diagnostic biomarkers. Immune infiltration and inflammation levels among the subtypes were assessed using a single-sample gene set enrichment analysis. Results A total of 15 key differential m6A regulators (RBM15B, ELAVL1, ALKBH5, METTL16, ZC3H13, RBM15, YTHDC1, YTHDC2, YTHDF3, HNRNPC, FMR1, LRPPRC, HNRNPA2B1, RBMX, FTO) were identified using the random forest classifier and were found to be highly correlated by PPI analysis. Two distinct RNA modification patterns (cluster A and B) were validated based on the expression levels of the 15 key m6A regulators. GO and KEGG annotations showed that immunity and inflammation pathways were enriched. Immune infiltration analysis revealed that cluster 2 had higher immune activation than cluster 1. Further analysis showed that cluster 2 had a higher inflammation level, with IL-4 and IL-33 showing differential expression (p < 0.05). Conclusion A set of 15 m6A RNA methylation regulators could alter the STEMI microenvironment to improve risk stratification and clinical treatment.

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Section: Discussionmentioning

confidence: 99%

Diagnostic biomarkers for ST-segment elevation myocardial infarction using RNA methylation regulators

Li,

Ma,

Zhao

et al. 2024

Egypt J Med Hum Genet

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“…6 Early DNA methylation studies have identified differentially methylated regions near genes encoding cytokines as well as other genes within interferon and mTOR signaling pathways, as being relevant in renal transplant rejection. 7,8 No such work has been performed in pediatric LT recipients.…”

Section: Introductionmentioning

confidence: 99%

“…We and others have shown that trait-associated and dynamic epigenetic variants are enriched in distal regulatory enhancer regions and we further showed that these features are also seen downstream of the transcription start sites (TSS)-both genomic regions being underrepresented on commercially available arrays. [5][6][7][8][9][10][11] To overcome this limitation, we implemented the methylC-capture sequencing (MCC-Seq) approach for customized DNA methylation profiling of millions of CpGs located in regulatory elements known to be active specifically in immune cells. 11,12 Specifically, this immune cell MCC-Seq panel covers (1) the majority of human gene promoters, blood-cell-lineage-specific enhancer regions and methylation footprint regions observed in peripheral blood, 12 (2) CpGs from Illumina Human Methylation 450 Bead Chips, and (3) published autoimmune-related SNPs as well as SNPs in their linkage disequilibrium regions with r 2 > 0.8.…”

mentioning

confidence: 99%

The role of dynamic DNA methylation in liver transplant rejection in children

Ningappa

Shao

Ashokkumar

et al. 2022

Preprint

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Background: Transcriptional regulation of liver transplant (LT) rejection may reveal novel predictive and therapeutic targets. Purpose: To test the role of differential DNA methylation in children with biopsy-proven acute cellular rejection (rejectors, R) after LT. Methods: Paired peripheral blood DNA samples were obtained before and after LT from 17 children, including 4R and 13 non-rejector (NR), and assayed with MethylC capture sequencing (MCC-Seq) approach covering 5 million CpGs in immune-cell specific regulatory elements. Differentially methylated CpGs (DMCs) were identified using generalized linear regression models adjusting for sex and age and merged into differentially methylated regions (DMR) comprising 3 or more DMCs. Results: Contrasting R vs NR, we identified 2238 DMCs in post-LT and 2620 DMCs in pre-LT samples, which clustered in 216 and 282 DMRs respectively. DMCs associated with R were enriched in enhancers and depleted in promoters. The proportion of hypomethylated versus hypermethylated DMRs increased from 22% to 48% (p<0.0001) in pre-LT vs. post-LT DMCs, respectively. The highest-ranked biological processes enriched in post-LT DMCs were antigen processing and presentation via MHC class I, MHC class I complex, and peptide binding (p<7.92E-17), respectively. Top-ranked DMRs mapped to genes which mediate B-cell receptor signaling (ADAP1) or regulate several immune cells (ARRB2) (p<3.75E-08). DMRs in MHC class I genes were enriched for SNPs which bind TFs, affect gene expression and splicing, or alter peptide-binding amino acid sequences. Conclusions: Dynamic methylation in distal regulatory regions reveals known transplant-relevant MHC-dependent rejection pathways, and identifies novel loci for future mechanistic evaluations in pediatric transplant subcohorts.

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“… 6 Early DNA methylation studies have identified differentially methylated regions (DMRs) near genes encoding cytokines as well as other genes within interferon and mammalian target of rapamycin signaling pathways, as being relevant in renal transplant rejection. 7 , 8 No such work has been performed in pediatric LT recipients.…”

Section: Introductionmentioning

confidence: 99%

“…We and others have shown that trait-associated and dynamic epigenetic variants are enriched in distal regulatory enhancer regions and we further showed that these features are also seen downstream of the transcription start sitesboth genomic regions being underrepresented on commercially available arrays. [5][6][7][8][9][10][11] To overcome this limitation, we implemented the methylC-capture sequencing (MCC-Seq) approach for customized DNA methylation profiling of millions of CpGs located in regulatory elements known to be active specifically in immune cells. 11,12 Specifically, this immune cell MCC-Seq panel covers (1) the majority of human gene promoters, blood-cell-lineage-specific enhancer regions and methylation footprint regions observed in peripheral blood, 12 (2) CpGs from Illumina Human Methylation 450 Bead Chips, and (3) published autoimmune-related single nucleotide polymorphisms (SNPs) and SNPs in their linkage disequilibrium regions with r 2 > 0.8.…”

Section: Introductionmentioning

confidence: 99%

The Role of Dynamic DNA Methylation in Liver Transplant Rejection in Children

Ningappa

Shao

Ashokkumar

et al. 2022

Transplantation Direct

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Background. Transcriptional regulation of liver transplant (LT) rejection may reveal novel predictive and therapeutic targets. The purpose of this article is to test the role of differential DNA methylation in children with biopsy-proven acute cellular rejection after LT. Methods. Paired peripheral blood DNA samples were obtained before and after LT from 17 children, including 4 rejectors (Rs) and 13 nonrejectors (NRs), and assayed with MethylC capture sequencing approach covering 5 million CpGs in immune-cell-specific regulatory elements. Differentially methylated CpGs (DMCs) were identified using generalized linear regression models adjusting for sex and age and merged into differentially methylated regions (DMRs) comprising 3 or more DMCs. Results. Contrasting Rs versus NRs, we identified 2238 DMCs in post-LT and 2620 DMCs in pre-LT samples, which clustered in 216 and 282 DMRs, respectively. DMCs associated with R were enriched in enhancers and depleted in promoters. Among DMRs, the proportion of hypomethylated DMRs increased from 61/282 (22%) in pre-LT to 103/216 (48%, P < 0.0001) in post-LT samples. The highest-ranked biological processes enriched in post-LT DMCs were antigen processing and presentation via major histocompatibility complex (MHC) class I, MHC class I complex, and peptide binding (P < 7.92 × 10 −17 ), respectively. Top-ranked DMRs mapped to genes that mediate B-cell receptor signaling (ADAP1) or regulate several immune cells (ARRB2) (P < 3.75 × 10 −08 ). DMRs in MHC class I genes were enriched for single nucleotide polymorphisms (SNPs), which bind transcription factors, affect gene expression and splicing, or alter peptide-binding amino acid sequences. Conclusions. Dynamic methylation in distal regulatory regions reveals known transplant-relevant MHCdependent rejection pathways and identifies novel loci for future mechanistic evaluations in pediatric transplant subcohorts.

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Consideration of IL-2, IFN-γ and IL-4 expression and methylation levels in CD4+ T cells as a predictor of rejection in kidney transplant

Cited by 6 publications

References 28 publications

Diagnostic biomarkers for ST-segment elevation myocardial infarction using RNA methylation regulators

Diagnostic biomarkers for ST-segment elevation myocardial infarction using RNA methylation regulators

The role of dynamic DNA methylation in liver transplant rejection in children

The Role of Dynamic DNA Methylation in Liver Transplant Rejection in Children

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