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Rheumatoid arthritis patients, both newly diagnosed and methotrexate treated, show more DNA methylation differences in CD4+ memory than in CD4+ naïve T cells

ABSTRACT: Rheumatoid arthritis patients, both newly diagnosed and methotrexate treated, show more DNA methylation differences in CD4+ memory than in CD4+ naïve T cells

PROVIDER: PRJNA560040 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9960910.fastq.gz	Fastqsanger.gz
	SRR9960920.fastq.gz	Fastqsanger.gz
	SRR9960930.fastq.gz	Fastqsanger.gz
	SRR9960940.fastq.gz	Fastqsanger.gz
	SRR9960950.fastq.gz	Fastqsanger.gz

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Rheumatoid arthritis patients, both newly diagnosed and methotrexate treated, show more DNA methylation differences in CD4+ memory than in CD4+ naïve T cells

Project description:Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N=11), methotrexate (MTX) treated RA patients (N=18), and healthy controls (N=9) matched for age, gender and smoking status. Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (+/- 500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbour both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.

2020-02-07 | GSE135770 | GEO

Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DNA Methylation Differences in CD4<sup>+</sup> Memory Than in CD4<sup>+</sup> Naive T Cells.

Project description:Background: Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N = 11), methotrexate (MTX) treated RA patients (N = 18), and healthy controls (N = 9) matched for age, gender and smoking status. Results: Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs. 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (±500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbor both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.

| S-EPMC7033478 | biostudies-literature

Gene expression profiles of CD4+ T cells before and after methotrexate treatment in rheumatoid arthritis patients [Microarray]

Project description:To understand the molecular mechanisms by which methotraxate improves the disease activity in rheumatoid arthritis, CD4+ T cells were obtained before and 3month after methotrexate treatment.

2022-05-20 | GSE176440 | GEO

Methotrexate treatment of newly diagnosed RA patients is associated with DNA methylation differences at genes relevant for disease pathogenesis and pharmacological action

Project description:Background: Methotrexate (MTX) is the first line treatment of rheumatoid arthritis (RA), and methylation changes in bulk T cells have been reported after treatment with MTX. We have investigated cell-type specific DNA methylation changes across the genome in naïve and memory CD4+ T cells before and after MTX treatment of RA patients. DNA methylation profiles of newly diagnosed RA patients (N=9) were assessed by reduced representation bisulfite sequencing. Results: We found that MTX treatment significantly influenced DNA methylation levels at multiple CpG sites in both cell populations. Interestingly, we identified differentially methylated sites annotated to two genes; TRIM15 and SORC2, previously reported to predict treatment outcome in RA patients when measured in bulk T cells. Furthermore, several of the genes, including STAT3, annotated to the significant CpG sites are relevant for RA susceptibility or the action of MTX. Conclusion: We detected CpG sites that were associated with MTX treatment in CD4+ naïve and memory T cells isolated from RA patients. Several of these sites overlap genetic regions previously associated with RA risk and MTX treatment outcome.

2021-11-11 | GSE188509 | GEO

MicroRNA expression differences in blood-derived CD19+ B cells of methotrexate treated rheumatoid arthritis patients

Project description:The aims of the study were to assess the global miRNA repertoire of peripheral blood CD19+ B cells, by high throughput sequencing, and to uncover miRNA expression differences between RA patients (newly-diagnosed and methotrexate treated) and healthy controls.

2021-04-28 | GSE168284 | GEO

Methotrexate Clearance

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Single cell analysis of newly diagnosed AML patients

Project description:Acute Myeloid Leukemia (AML) is a heterogenous disease characterized by immature blasts at different maturation stage. We used single cell sequencing technique to analyze newly diagnosed AML patients.

2023-12-18 | GSE239721 | GEO

Gene expression profiles of CD4+ T cells before and after methotrexate treatment in rheumatoid arthritis patients [Microarray]

Project description:Gene expression profiles of CD4+ T cells before and after methotrexate treatment in rheumatoid arthritis patients [Microarray]

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Caco2 response to methotrexate, lactoferrin, and methotrexate-lactoferrin co-exposure

Project description:bulk sequencing outputs of Caco2 cells after exposure to permeability modifying and permeability rescuing agents. To identify the molecular drivers for methotrexate-induced barrier dysfunction, we conducted RNA sequencing on Caco2 spheroids treated with methotrexate and lactoferrin. Given our observation that barrier function was compromised as early as 4-6 hours after exposure to methotrexate, we isolated RNA from spheroids 4-hour post-treatment to capture the transcriptional events responsible for initiating the processes.

2020-01-10 | GSE140066 | GEO

Gene expression of monocytes from rheumatoid arthritis patients treated with bDMARDs and methotrexate.

Project description:It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic Disease-Modifying AntiRheumatic Drugs (bDMARDs) available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFalpha or abatacept, and from healthy donors. Differential expression analysis of whole-genome transcriptomics yielded a list of regulated genes suitable for functional annotation enrichment analysis. Specifically, abatacept, tocilizumab and anti-TNFalpha cohorts were separately compared with methotrexate using a rank-product-based statistical approach, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively.

2023-03-09 | GSE224330 | GEO

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