The epigenetic impact of the exposome on Sjögren's disease. A systematic review

Objectives.Sjgren's disease (SjD) is a complex systemic autoimmune disorder with a multistep pathogenesis driven by the interplay of genetic, epigenetic, hormonal, and environmental factors.Even though genetic predisposition is clearly associated with disease susceptibility, it cannot fully explain its pathophysiology.Hormonal fluctuations and various components of the exposome are also considered critical contributors to disease onset and progression.Environmental exposures can induce heritable changes that modulate gene expression without affecting the underlying DNA sequence, known as epigenetic alterations.Methods.A comprehensive literature search was conducted across major databases (PubMed, MEDLINE, Embase and Web of Science).No publication date restrictions were applied, but only articles written in English were considered.Studies were eligible for inclusion if they investigated any environmental exposure in association with epigenetic modifications in SjD, using human, animal (e.g., mice), or in vitro/ in vivo models.Results.Epigenetic mechanisms, including DNA methylation, histone modifications, and dysregulation of non-coding RNAs (nc-RNAs), are increasingly recognised as central to SjD pathogenesis.These alterations may serve as a crucial link between the exposome and the onset of autoimmune processes by mediating the immune system's response to external stimuli.Consequently, they may promote aberrant immune activation, leading to both glandular and extra-glandular manifestations, and may increase the risk of lymphomagenesis through chronic Bcell stimulation within affected issues.Conclusions.Despite notable advances, further research is warranted to elucidate how specific environmental and epigenetic factors interact in genetically susceptible individuals.This systematic review also highlights the potential of epigenetic modifications as biomarkers to enhance diagnostic accuracy and design targeted, individualised therapies based on precision medicine approaches.