Abstract
ObjectivesSystemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens and by chronic inflammation. Although the etiology of SLE remains unclear, the influence of environment factors, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, is generally considered as main players in the pathogenesis of SLE. We studied DNA methyltransferases’ (DNMTs) type 1, 3A and 3B transcript levels in peripheral blood mononuclear cells from patients diagnosed with systemic lupus erythematosus and from the healthy control subjects. Furthermore, the association of DNMT1, DNMT3A, and DNMT3B mRNA levels with gender, age, and major clinical manifestations was analyzed.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from 32 SLE patients and 40 healthy controls. Reverse transcription and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine DNMT1, DNMT3A, and DNMT3B mRNA expression levels.ResultsSignificantly lower DNMT1 (p = 0.015543) and DNMT3A (p = 0.003652) transcript levels in SLE patients were observed compared with healthy controls. Nevertheless, the DNMT3B mRNA expression levels were markedly lower compared with DNMT1 and DNMT3A, both in PBMCs from affected patients and those from control subjects. Furthermore, the DNMT1 transcript levels were positively correlated with SLE disease activity index (SLEDAI) (rs = 0.4087, p = 0.020224), while the DNMT3A transcript levels were negatively correlated with patients age (rs = −0.3765, p = 0.03369).ConclusionsOur analyses confirmed the importance of epigenetic alterations in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, such as phototosensitivity and arthritis, might be associated with the dysregulation of DNA methyltransferases’ mRNA expression levels.
Highlights
Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disorder with a spectrum of clinical manifestations and outcomes [1]
St., 61‐545 Poznań, Poland lower compared with DNMT1 and DNMT3A, both in Peripheral blood mononuclear cells (PBMCs) from affected patients and those from control subjects
Our analyses confirmed the importance of epigenetic alterations in SLE etiology
Summary
Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disorder with a spectrum of clinical manifestations and outcomes [1]. SLE, such as many autoimmune diseases, occurs more frequently in women, and the reason for this female preponderance is suggested role of female sex hormones [7]. Multiple studies have demonstrated a pivotal role of epigenetic mechanisms of gene regulation in SLE etiology. Methylation of deoxycytosine (dC) bases in CG pairs, referred to as DNA methylation, is the most common epigenetic mechanisms of gene regulation. Less than 10% of CpGs occur in CG-dense regions that are termed CpG islands [11] Their transcriptionally repressive activity is generally ascribed to promoter regions [12]. DNA methylation contributes to systemic lupus erythematosus predisposition and is generally considered as key player in the pathogenesis of SLE [13]. Twin studies confirmed the importance of DNA demethylation in human lupus [14]
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