DNA Methylation of CD70 Promoter in Juvenile Systemic Lupus Erythematosus

Keshavarz-Fathi, Mahsa; Sanati, Golshid; Sadr, Maryam; Mohebbi, Bahareh; Ziaee, Vahid; Rezaei, Nima

doi:10.1080/15513815.2020.1764681

Cited by 8 publications

(10 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In adult-onset JSLE, hypomethylation of CD70 (encoding for TNFSF7-tumour necrosis factor ligand superfamily member 7) in CD4+ T cells results in increased gene expression and subsequently enhanced B-cell stimulation that contributes to the pathogenesis of SLE [95][96][97][98]. Findings may be specific to CD4+ T cells, as Keshavarz-Fathi et al did not observe statistically significant differences in CD70 promoter methylation of peripheral blood mononuclear cells (PBMCs) from patients with jSLE [99].…”

Section: Epigenetic Factorsmentioning

confidence: 99%

Systemic Lupus Erythematosus in Children and Young People

2021

View full text Add to dashboard Cite

Purpose of Review Juvenile-onset systemic lupus erythematosus ((j)SLE) is an autoimmune/inflammatory disease that results in significant damage and disability. When compared to patients with disease onset in adulthood, jSLE patients exhibit increased disease activity, damage and require more aggressive treatments. This manuscript summarises age-specific pathogenic mechanisms and underscores the need for age group–specific research, classification and treatment. Recent Findings Genetic factors play a significant role in the pathophysiology of jSLE, as > 7% of patients develop disease as a result of single gene mutations. Remaining patients carry genetic variants that are necessary for disease development, but require additional factors. Increased ‘genetic impact’ likely contributes to earlier disease onset and more severe phenotypes. Epigenetic events have only recently started to be addressed in jSLE, and add to the list of pathogenic mechanisms that may serve as biomarkers and/or treatment targets. To allow meaningful and patient-oriented paediatric research, age-specific classification criteria and treatment targets require to be defined as currently available tools established for adult-onset SLE have limitations in the paediatric cohort. Summary Significant progress has been made in understanding the pathophysiology of jSLE. Meaningful laboratory and clinical research can only be performed using age group–specific tools, classification criteria and treatment targets.

show abstract

Section: Epigenetic Factorsmentioning

confidence: 99%

Systemic Lupus Erythematosus in Children and Young People

2021

View full text Add to dashboard Cite

show abstract

“…13,78 Sorted blood cells encompassing neutrophils, low-density granulocytes, CD3 + , CD4 + , CD8 + , and B lymphocytes were starting materials in 20 studies. The most researched genes in promoter regions were IFI44L , 53,58,62,71,73,78,79,85 CD70 ( TNFSF7 ), 55,59,68 FOXP3 , 61,68,81 and MX1 . 52,53,78 Also, six studies evaluated methylation levels at the interspersed repetitive sequences (IRSs) which are CpG-rich subsuming LINE-1, Alu, and human endogenous retroviruses (HERV)-E and HERV-K. 63–65,70,77,87 Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic power (area under the curve; AUC) of methylation levels were only reported for IFI44L in five studies 58,62,71,73,79 (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The most important characteristics of the 44 eligible studies are summarized in Table 1. Given the effect of ethnicity (genetic background) on methylation pattern, 40,51 22 studies were performed in China, seven in USA, 14,[52][53][54][55][56][57] five in Iran, [58][59][60][61][62] three in Thailand, [63][64][65] two in Taiwan, 13,66 and one each in jointly USA and South Korea, 67 South Africa, 68 India, 24 United kingdom, 69 and France. 70 In all, 3471 SLE patients and 1028 healthy subjects were recruited for studies.…”

Section: Resultsmentioning

confidence: 99%

“…70 In all, 3471 SLE patients and 1028 healthy subjects were recruited for studies. They enrolled SLE patients and healthy controls with no self-history or family history of autoimmune, [58][59][60][61][62][63][64][71][72][73][74][75] rheumatologic, [58][59][60]76 inflammatory, [58][59][60][61]72 infectious, 62,[71][72][73]76,77 cardiovascular, 71,73,76 chronic, 78 connective tissue, 74 and neurological or psychiatric 74,75 diseases as well as cancer, 62,63,[71][72][73]76 substance abuse, 74,75 hepatitis B, tuberculosis, AIDS, and fever. 72 Only one study stated that SLE patients were unrelated and SLE-free controls were without any kinship with patients.…”

Section: Resultsmentioning

confidence: 99%

“…While in four studies, the methylation patterns of pediatric or juvenile SLE (JSLE) patients in whom the symptoms initiate under the age of 18 were examined. [59][60][61]77 In all studies, the control group was matched by age, sex, and ethnicity to the patient group. Although, in one study conducted by Hanaei et al, the control subjects were not matched by age with the patients.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

DNA methylation alterations in systemic lupus erythematosus: A systematic review of case-control studies

Ehtesham

Kavashkohie

Mazhari

et al. 2022

Lupus

View full text Add to dashboard Cite

Background Traditionally, the diagnosis and monitoring of disease activity in systemic lupus erythematosus (SLE) are contingent upon clinical manifestations and serological markers. However, researchers are struggling to find biomarkers with higher sensitivity and specificity. DNA methylation has been the most studied epigenetic feature in SLE. So, in this study, we performed a systematic review of studies about DNA methylation alterations in SLE patients compared to healthy controls. Methods By searching PubMed, Scopus, and Google Scholar up to July 2022, all case-control studies in which DNA methylation of specific genes was assessed by a non-high-throughput technique and passed the quality of bias assessment were included. Results In total, 44 eligible studies underwent a data extraction process. In all, 3471 SLE patients and 1028 healthy individuals were included. Among the studies that reported the patients’ gender ( n = 2853), 89.41% were female and 10.59% were male. Forty studies have been conducted on adult patients. The number of works on fractionated and unfractionated blood cells was almost equal. In this regard, 22 studies were conducted on whole blood or peripheral blood mononuclear cells and two studies on unfractionated white blood cells. Sorted blood cells were biological sources in 20 studies. The most investigated gene was IFI44L. Sensitivity, specificity, and diagnostic power of methylation levels were only reported for IFI44L in five studies. The most employed methylation profiling method was bisulfite sequencing polymerase chain reaction. The correlation between methylation patterns and clinical parameters was explored in 22 studies, which of them 16 publications displayed a remarkable association between DNA methylation status and clinical indices. Conclusions The methylation status of some genes especially IFI44L, FOXP3, and MX1 has been suggested as promising SLE biomarkers. However, given the conflicting findings between studies because of potential confounders such as different sample types, methylation profiling methods, and ethnicity as well as shared DNA methylation patterns of SLE and other autoimmune diseases, DNA methylation biomarkers are currently not reliable diagnostic biomarkers and do not represent surrogate markers of SLE disease activity. Future investigations on a larger scale with the discarding of limitations of previous studies would probably lead to a consensus.

show abstract

Systemic lupus erythematosus: latest insight into etiopathogenesis

et al. 2023

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.

show abstract

DNA Methylation of CD70 Promoter in Juvenile Systemic Lupus Erythematosus

Cited by 8 publications

References 47 publications

Systemic Lupus Erythematosus in Children and Young People

Systemic Lupus Erythematosus in Children and Young People

DNA methylation alterations in systemic lupus erythematosus: A systematic review of case-control studies

Systemic lupus erythematosus: latest insight into etiopathogenesis

Contact Info

Product

Resources

About