The role of epigenetics in childhood autoimmune diseases with hematological manifestations

Abstract

Autoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment, and the underlying pathogenetic mechanisms remain unknown. Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases. In recent years, study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors. Various mechanisms, including DNA methylation, histone modifications (chromatin remodeling), and noncoding RNAs (ncRNAs), have been studied extensively in the context of autoimmune diseases. This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations, based on epigenetic studies in children with primary immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), and juvenile idiopathic arthritis (JIA). Research findings indicate that methylation changes in genes expressed on T cells, modifications at a variety of histone sites, and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases. These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers. Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders, and possible novel treatment options.

Scoping Review on Epigenetic Mechanisms in Primary Immune Thrombocytopenia

“…H3K9 methylation is known to be a gene-repressive function that mediates the silencing of invasive and repetitive sequences by preventing the expression of aberrant gene products and the activation of transposition and is associated with a condensed heterochromatin state [ 145 , 146 , 147 ]. Hypomethylation in this region can result in marked genomic instability [ 148 ].…”

Updates on the role of epigenetics in familial mediterranean fever (FMF)

“…Histone modifications have been found to play a role in the activation of the NLRP3 inflammasome and subsequently in the manifestation of multiple autoimmune and autoinflammatory disorders, such as systemic lupus erythematosus [ 47 ], rheumatoid arthritis [ 48 ], Behçet disease (BD) [ 49 ], atherosclerosis, and Alzheimer’s disease [ 50 ]. Nevertheless, to date, no study has investigated the role of histone modifications in FMF, despite the relevant implication of the NLRP3 inflammasome in the pathogenesis of this disease.…”

Incidence and risk factors of systemic lupus erythematosus in patients with primary immune thrombocytopenia: a systematic review and meta-analysis

“…Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody production and multiorgan involvement, which involves multiple systems and organs, especially the kidneys and central nervous system, resulting in worse prognoses than primary ITP. Several articles have demonstrated that ITP and SLE share a common genetic predisposition ( Fanouriakis, Bertsias & Boumpas, 2020 ; Gkoutsias & Makis, 2022 ), and some patients with primary ITP may develop into SLE during follow-up ( Hazzan et al, 2006 ; Song et al, 2022 ). However, there are few related studies and the predictive risk factors remain unclear.…”