







































_____________________________________________________________________________________________________ 
 
*Corresponding author: E-mail: ayodeleadeli101@gmail.com;   
 
Cite as: Fagbemi Oluwaseyi Ajibola, and Adedoyin Elizabeth Ayodele. 2025. “Epigenetic Dysregulation and Its Role in 
Immune-Mediated Diseases”. Asian Journal of Immunology 8 (1):230–241. https://doi.org/10.9734/aji/2025/v8i1174. 
 
 

 
 

Asian Journal of Immunology 
 
Volume 8, Issue 1, Page 230-241, 2025; Article no.AJI.144830 
 

 
 

 

 

Epigenetic Dysregulation and its Role 
in Immune-Mediated Diseases 

 
Fagbemi Oluwaseyi Ajibola a  

and Adedoyin Elizabeth Ayodele b* 
 

a Department of Human Anatomy, College of Medicine and Surgery, Federal University Lokoja,  
Kogi State, Nigeria. 

b Department of Microbiology, Federal University Oye Ekiti, Ekiti State, Nigeria. 
 

Authors’ contributions  
 

This work was carried out in collaboration between both authors. Both authors read and approved the 
final manuscript. 

 
Article Information 

 
DOI: https://doi.org/10.9734/aji/2025/v8i1174 

 
Open Peer Review History: 

This journal follows the Advanced Open Peer Review policy. Identity of the Reviewers, Editor(s) and additional Reviewers,  
peer review comments, different versions of the manuscript, comments of the editors, etc are available here: 

https://pr.sdiarticle5.com/review-history/144830 

 
 

Received: 18/07/2025 
Published: 27/09/2025 

 
 

ABSTRACT 
 

Immune-mediated diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus 
(SLE), multiple sclerosis (MS) and Inflammatory Bowel Disease (IBD: Crohn's Disease & Ulcerative 
Colitis) represent a significant global health burden characterized by a loss of immune tolerance 
and chronic inflammation. While genetic predisposition plays a crucial role, it does not fully account 
for disease pathogenesis, onset, or flare-ups. The emerging field of epigenetics provides a critical 
mechanistic link between genetic susceptibility and environmental triggers. This review synthesizes 
current evidence on how dysregulation of key epigenetic mechanisms, DNA methylation, histone 
modifications, and non-coding RNA expression, contributes to the breakdown of immune 
homeostasis. We detail the aberrant epigenetic landscapes in specific immune cell subsets (e.g., T 
cells, B cells, macrophages) across major autoimmune disorders. Furthermore, we explore the 
potential of epigenetic modifications as novel biomarkers for diagnosis, prognosis, and disease 
activity monitoring. Finally, we discuss the promising therapeutic avenue of "epigenetic therapy," 

Review Article 

https://doi.org/10.9734/aji/2025/v8i1174
https://pr.sdiarticle5.com/review-history/144830


 
 
 
 

Ajibola and Ayodele; Asian J. Immunol., vol. 8, no. 1, pp. 230-241, 2025; Article no.AJI.144830 
 
 

 
231 

 

repurposing existing drugs and developing new compounds to reverse pathogenic epigenetic marks 
and restore immune tolerance. 
 

 

Keywords: Epigenetics; autoimmunity; DNA methylation; histone modification; non-coding RNA; 
rheumatoid arthritis; systemic lupus erythematosus; multiple sclerosis; biomarkers; 
epigenetic therapy. 

 

1. INTRODUCTION 
 
Immune-mediated inflammatory diseases 
(IMIDs), encompassing a broad spectrum of 
conditions such as rheumatoid arthritis (RA), 
systemic lupus erythematosus (SLE), multiple 
sclerosis (MS), and inflammatory bowel disease 
(IBD), represent a formidable challenge to global 
public health. These chronic, debilitating 
disorders are characterized by a pathological 
breakdown of self-tolerance, leading to 
uncontrolled immune activation against specific 
tissues or systemically, resulting in persistent 
inflammation and organ damage (Wilkinson & 
Shapiro, 2024). The collective prevalence of 
IMIDs is estimated to affect 5-10% of the 
population in developed nations, posing a 
significant economic and social burden due to 
long-term disability, reduced quality of life, and 
the need for lifelong medical management 
(Stroeks et al., 2025)  
 
The etiological landscape of autoimmunity has 
long been conceptualized through the lens of 
genetic predisposition interacting with 
environmental triggers. The advent of genome-
wide association studies (GWAS) has been 
instrumental, identifying over hundreds of 
susceptibility loci across various IMIDs. These 
studies have robustly confirmed the paramount 
importance of the major histocompatibility 
complex (MHC) region and highlighted key 
pathways involved in immune cell signaling, 
cytokine production, and lymphocyte activation 
(Ausserwinkler et al., 2025; Arneth, 2024). 
However, a critical paradox emerged from this 
genetic data: the identified risk alleles, while 
statistically significant, often confer only a 
modest increase in relative risk and    exhibit low 
penetrance. This is most strikingly evidenced by 
the significant discordance rates observed in 
monozygotic (identical) twins, who share nearly 
100% of their genetic sequence. For example, 
concordance rates for SLE, RA, and MS typically 
range from only 25% to 40%, leaving a 
substantial portion of disease risk unexplained by 
genetics alone (Khan et al., 2024; Ates et al., 
2025). This compelling "heritability gap" strongly                
implies that non-genetic factors play a dominant 

role in determining whether a genetically 
susceptible individual will ultimately develop 
clinical disease. 
This gap is bridged by epigenetics, a discipline 
that has revolutionized our understanding of 
gene regulation. Epigenetics refers to the study 
of heritable changes in gene expression and 
cellular phenotype that occur without alterations 
to the underlying DNA nucleotide sequence (Lin 
et al.,2024; Gibson et al., 2022). These 
mechanisms, primarily DNA methylation, histone 
modifications, and non-coding RNA-associated 
gene silencing, act as dynamic regulators of 
chromatin architecture, determining the 
accessibility of genetic information to the 
transcriptional machinery. Crucially, the 
epigenetic landscape is plastic and can be 
actively shaped by a myriad of environmental 
exposures, including infectious agents (e.g., 
Epstein-Barr virus), tobacco smoke, hormonal 
changes, dietary components, and pollutants 
(Kwon et al., 2024; Kaszycki and Kim, 2025). 
These factors can initiate stable epigenetic 
reprogramming within immune cells, potentially 
leading to the sustained overexpression of pro-
inflammatory genes or the silencing of key 
immunoregulatory pathways. 
 

This review manuscript synthesizes current 
evidence positing that epigenetic dysregulation 
serves as the crucial mechanistic link between 
genetic susceptibility and environmental triggers 
in the pathogenesis of immune-mediated 
diseases. We will detail the aberrant epigenetic 
patterns, the "epigenome" characteristic of major 
IMIDs, focusing on specific immune cell subsets. 
Furthermore, we will explore the profound 
translational implications of this field, discussing 
the potential of epigenetic marks as novel 
biomarkers for diagnosis and prognostication and 
surveying the promising frontier of epigenetic-
based therapeutics aimed at reversing 
pathogenic marks and restoring immune 
homeostasis. 
 

2. FUNDAMENTAL EPIGENETIC 
MECHANISMS 

 

Epigenetic regulation provides a dynamic and 
heritable layer of control over gene expression, 



 
 
 
 

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enabling cellular differentiation and plasticity in 
response to environmental cues without altering 
the primary DNA sequence. In the immune 
system, these mechanisms are paramount for 
the development, activation, and termination of 
responses, ensuring a precise balance between 
effective pathogen clearance and self-tolerance. 
The dysregulation of these processes is a 
cornerstone of autoimmune pathology. The three 
primary, interconnected epigenetic mechanisms 
are DNA methylation, histone modifications, and 
non-coding RNA-associated silencing. restoring 
immune homeostasis. 
 

2.1 DNA Methylation 
 
DNA methylation is the most extensively studied 
epigenetic modification in mammals. It involves 
the covalent addition of a methyl group to the 5' 
position of a cytosine ring, primarily within CpG 
dinucleotide sequences. Dense clusters of CpG 
sites, known as CpG islands, are often found in 
gene promoter regions. Methylation of these 
islands typically leads to transcriptional 
repression by physically impeding the binding of 
transcription factors and by recruiting proteins 
such as methyl-CpG-binding domain proteins 
(MBDs), which then attract histone deacetylases 
and other chromatin-remodeling complexes to 
establish a closed, silent chromatin state (Harris 
et al, 2025; Smith et al., 2025). 
 
The establishment and maintenance of DNA 
methylation patterns are catalyzed by a family of 
enzymes called DNA methyltransferases 
(DNMTs). DNMT3A and DNMT3B are 
responsible for de novo methylation, setting up 
new methylation patterns during embryonic 
development. DNMT1, the maintenance 
methyltransferase, faithfully copies methylation 
patterns to the daughter strand during DNA 
replication, ensuring heritability of the              
epigenetic mark through cell divisions (Sarre et 
al., 2025). 
 

In the context of immunity, DNA methylation is 
critical for processes such as X-chromosome 
inactivation, genomic imprinting, and the 
silencing of endogenous retroviral elements. 
Crucially, it governs lymphocyte lineage 
commitment and function. For example, the 
differentiation of naïve CD4+ T cells into distinct 
effector subsets (Th1, Th2, Th17) and 
immunosuppressive regulatory T cells (Tregs) is 
orchestrated by precise changes in the 
methylation status of key cytokine and 
transcription factor genes (Roy et al., 2025). A 

hallmark of many autoimmune diseases, 
particularly SLE, is a state of global DNA 
hypomethylation in T cells, which promotes the 
aberrant overexpression of autoimmune-
associated genes (e.g., ITGAL (CD11a) and 
TNFSF7 (CD70)), alongside locus-specific 
hypermethylation events that may silence 
protective genes (Deng et al., 2024) 
 

2.2 Histone Post-Translational Modifica-
tions 

 
Histones are the core protein components of 
nucleosomes, around which DNA is wrapped. 
Their N-terminal tails are subject to over 100 
different post-translational modifications (PTMs), 
including acetylation, methylation, 
phosphorylation, ubiquitination, and sumoylation. 
These PTMs alter the electrostatic charge of 
histones and serve as docking sites for other 
proteins, collectively influencing chromatin 
accessibility and gene expression (Nie et al., 
2024). 
 
The most well-characterized modifications are: 
 
Acetylation/deacetylation: Catalyzed by 
histone acetyltransferases (HATs) and histone 
deacetylases (HDACs), respectively. Acetylation 
neutralizes the positive charge on lysine 
residues, reducing the affinity between histones 
and the negatively charged DNA backbone. This 
results in a more open, transcriptionally 
permissive chromatin structure (euchromatin). 
Deacetylation has the opposite effect, promoting 
chromatin condensation and gene silencing 
(heterochromatin) (Chen et al., 2024). 
 
Methylation: Catalyzed by histone 
methyltransferases (HMTs) and removed by 
histone demethylases (HDMs). The functional 
outcome of methylation is highly context-
dependent, varying by the specific lysine or 
arginine residue modified and the degree of 
methylation (mono-, di-, or tri-methylation). For 
instance, trimethylation of histone H3 lysine 4 
(H3K4me3) is a mark of active promoters, while 
trimethylation of H3 lysine 27 (H3K27me3) is a 
repressive mark associated with facultative 
heterochromatin (Chen et al., 2024). 
 

The "histone code" hypothesis posits that these 
combinations of modifications act sequentially or 
in concert to form a complex language that 
dictates specific functional outcomes for a 
chromosomal region (Ueberheide et al., 2024). In 
immune cells, activating marks like H3K4me3 



 
 
 
 

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and H3K9ac are enriched at the promoters of 
highly expressed cytokine genes (e.g., IFNG, 
IL4, IL17), while repressive marks like 
H3K27me3 help silence alternative lineage 
genes during T-cell differentiation, ensuring 
stable effector cell identity (Jay et al., 2025). 
 

2.3 Non-Coding RNAs (ncRNAs) 
 
Non-coding RNAs represent a vast and diverse 
class of functional RNA molecules that are 
transcribed from the genome but not translated 
into proteins. They act as crucial epigenetic 
regulators, primarily at the post-transcriptional 
level. 
 
MicroRNAs (miRNAs): These are short (~22 
nucleotides), single-stranded RNAs that              
regulate gene expression by binding to 
complementary sequences in the 3' untranslated 
regions (UTRs) of target messenger RNAs 
(mRNAs). This binding typically leads to                
mRNA degradation or translational repression.                          
A single miRNA can target hundreds of                
mRNAs, allowing it to fine-tune entire genetic 
networks. In immunology, miRNAs are 
indispensable regulators of immune cell 
development, proliferation, differentiation, and 
function. For example, miR-155 is a pro-
inflammatory miRNA that promotes Th1 and 
Th17 responses, while miR-146a acts as a 
critical negative feedback regulator of NF-κB 
signaling and is often dysregulated in 
autoimmunity (Shaheen et al., 2024; Mehta et al., 
2025). 
 
Long Non-Coding RNAs (lncRNAs): These are 
transcripts longer than 200 nucleotides with 
limited protein-coding potential. They exert their 
regulatory functions through a variety of 
mechanisms: as scaffolds for chromatin-
modifying complexes, guides for their localization 
to specific genomic loci, decoys for transcription 
factors, or sponges that sequester miRNAs. The 
lncRNA MALAT1, for instance, has been 
implicated in regulating alternative splicing and 
gene expression in immune cells, while others 
like TMEVPG1 (NeST) can influence epigenetic 
states to control interferon-γ expression 
(Antonazzo et al., 2024). 
 
These three mechanisms do not operate in 
isolation but form a highly integrated regulatory 
network. DNA methylation can influence histone 
modification patterns, and both can be guided by 
ncRNAs. Conversely, histone modifications can 
regulate the expression of ncRNAs. This 

complex crosstalk ensures precise 
spatiotemporal control of the gene expression 
programs that dictate immune cell identity and 
function, and its disruption lies at the heart of 
epigenetic dysregulation in disease (Kong et al., 
2024). 
 

3. EPIGENETIC DYSREGULATION IN 
SPECIFIC IMMUNE-MEDIATED 
DISEASES 

 
The overarching principles of epigenetic 
regulation become profoundly altered in immune-
mediated diseases. The following section details 
the disease-specific epigenetic landscapes that 
contribute to pathogenesis, moving from 
systemic autoimmunity to organ-specific 
disorders. 
 

3.1 Systemic Lupus Erythematosus (SLE) 
 
SLE is arguably the best-studied autoimmune 
disease from an epigenetic perspective and                   
is characterized by a profound state of global 
DNA hypomethylation in CD4+ T cells and                 
other immune cells. This hypomethylation   
mirrors the epigenetic state of activated, 
proliferating T cells and leads to the 
overexpression of genes normally silenced in 
resting lymphocytes, such as perforin (PRF1), 
the T-cell adhesion molecule ITGAL (CD11a), 
and the co-stimulatory molecule TNFSF7 (CD70) 
(Ribeiro et al., 2024; Araki & Mimura, 2024). This 
aberrant overexpression promotes autoreactive 
T-cell help to B cells, driving autoantibody 
production. 
 

Mechanism of hypomethylation: The root 
cause involves impaired ERK signaling pathway 
signaling, leading to reduced expression and 
translocation of DNMT1. This results in             
passive demethylation during cell division. 
Furthermore, oxidative stress and elevated levels 
of nitric oxide in SLE patients can directly          
inhibit DNMT enzymatic activity (Somers et al., 
2024). 
 

Histone modifications: SLE T cells exhibit a 
shift towards a transcriptionally permissive 
chromatin state. This is characterized by globally 
decreased levels of the repressive mark 
H3K27me3 and increased levels of activating 
marks like H3K18ac and H3K4me3 at the 
promoters of key interferon-stimulated genes 
(ISGs) and inflammatory cytokines, amplifying 
the type I interferon signature that is a hallmark 
of SLE (Zhang et al., 2024). 



 
 
 
 

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ncRNAs: A distinct miRNA signature is present 
in SLE patient blood and tissues. miR-146a, a 
negative regulator of the interferon pathway, is 
under expressed, contributing to unchecked IFN 
production. Conversely, miR-21 and miR-148a 
are overexpressed; they promote autoimmunity 
by targeting DNMT1, creating a vicious cycle of 
DNA hypomethylation, and by dampening 
negative regulatory pathways (Royo et al., 2025). 
 

3.2 Rheumatoid Arthritis (RA) 
 

In RA, epigenetic dysregulation is most 
prominently studied in the hyperplastic, invasive 
synovial tissue, particularly in fibroblast-like 
synoviocytes (FLS), which develop an 
aggressive, "transformed-like" phenotype that 
drives joint destruction. 
 

DNA methylation: RA-FLS exhibit a unique and 
stable "methylation signature" that distinguishes 
them from osteoarthritis FLS and is present even 
in early disease. Key changes include: 
 

Hypomethylation of genes encoding matrix-
degrading enzymes (MMP3, MMP9), 
chemokines (CXCL12), and critical signaling 
molecules (STAT3, IRF5), leading to their 
overexpression and promoting inflammation, 
angiogenesis, and tissue invasion (Prideaux et 
al., 2024). 
 

Hypermethylation of genes that normally promote 
apoptosis or cell cycle arrest, such as 
TNFRSF25 (DR3) and BCL2L11 (BIM), 
conferring resistance to cell death and 
contributing to synovial hyperplasia (Svendsen et 
al., 2025). 
 

Histone modifications: The balance of 
HAT/HDAC activity is skewed in RA. While some 
HDACs are downregulated, class I and II HDAC 
activity is generally increased in RA synovium, 
contributing to the suppression of anti-
inflammatory genes. Conversely, HAT activity is 
also elevated, promoting the expression of pro-
inflammatory genes like IL6 and TNF (Enayati et 
al., 2024). 
 

ncRNAs: miR-155 is highly expressed in RA 
synovial fluid and tissue, where it promotes 
macrophage activation and Th17 cell 
differentiation. miR-146a is also upregulated but 
may act in a feedback inhibitory role that is 
ultimately insufficient to control inflammation. 
miR-124a is significantly downregulated, leading 
to increased activation of the monocyte 
chemoattractant CCL2 (Seyedi et al., 2024). 

3.3 Multiple Sclerosis (MS) 
 

Epigenetic mechanisms in MS are critical for 
determining the fate of T cells, pushing 
differentiation towards pro-inflammatory Th1 and 
Th17 lineages and away from immunoregulatory 
Tregs. 
 

DNA methylation: Genome-wide studies reveal 
significant differences in DNA methylation 
patterns in CD4+ T cells, CD8+ T cells, and B 
cells of MS patients compared to controls. 
Intriguingly, the strongest MS-associated genetic 
risk variant, HLA-DRB1, also displays MS-
specific methylation patterns, suggesting a 
complex gene-environment interaction where 
epigenetics modulates the effect of the primary 
genetic risk factor (Elbahrawi et al., 2024). Key 
hypomethylated loci are associated with T-cell 
activation and adhesion pathways. 
 

Histone modifications: HDACs and sirtuins 
(SIRT1, a class III HDAC) are key regulators of 
T-cell plasticity in MS. SIRT1 deficiency has 
been linked to hyperacetylation of the 
transcription factor FOXO1, impairing Treg 
function and promoting a pro-inflammatory T-cell 
state. Furthermore, inhibitors of HDACs have 
been shown to ameliorate disease in 
experimental autoimmune encephalomyelitis 
(EAE), the mouse model of MS, by promoting 
Treg development (Xie et al., 2025). 
 

ncRNAs: Circulating miRNAs serve as promising 
biomarkers. miR-326 expression correlates with 
disease severity and promotes Th17 
differentiation. miR-17-92 cluster members are 
dysregulated, impacting T-cell proliferation. 
Serum levels of miR-155 and miR-301a are also 
elevated and associated with active disease (Xie 
et al., 2025) 
 

3.4 Inflammatory Bowel Disease (IBD: 
Crohn's Disease & Ulcerative Colitis) 

 

The intestinal epithelium and mucosal immune 
system in IBD patients display widespread 
epigenetic alterations induced by the luminal 
environment (microbiome, nutrients). 
 

DNA methylation: Studies on intestinal mucosal 
biopsies reveal hundreds of differentially 
methylated regions. Crohn's disease is often 
associated with hypermethylation and silencing 
of the SOCS1 gene, a negative regulator of 
cytokine signaling, leading to enhanced 
JAK/STAT signaling. In ulcerative colitis, the TNF 
gene promoter is often hypomethylated, 
contributing to its excessive production 
(Mahurkar‐Joshi et al., 2025). 



 
 
 
 

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Table 1. Summary of key epigenetic alterations in major immune-mediated diseases 
 

Disease Cell type/ 
tissue 

DNA methylation changes Histone 
modifications 

Key ncRNAs 
involved 

SLE CD4+ T 
cells 

Global hypomethylation; 
Hypomethylation 
of CD11a, CD70 

Increased H3/H4 
acetylation 

↓ miR-146a, ↑ miR-21, 
↑ miR-155 

RA Synovial 
FLS 

Hypomethylation 
of CXCL12, IL6; 
Hypermethylation of DR3, BIM 

Increased HDAC 
activity 

↑ miR-155, ↑ miR-203, 
↑ miR-124a 

MS CD4+ T 
cells, 
PBMCs 

Differential methylation at HLA 
& non-HLA loci 

Altered 
HDAC/SIRT 
expression 

↑ miR-326, ↑ miR-155, 
↓ miR-17-92 

IBD Intestinal 
mucosa 

Hypermethylation 
of SOCS1 (Crohn's); 
Hypomethylation of TNF 

Altered 
HAT/HDAC 
balance 

↑ miR-21, ↑ miR-29, 
miR-196 dysregulation 

 
Histone Modifications: Butyrate, a short-chain 
fatty acid produced by commensal gut                   
bacteria, is a natural HDAC inhibitor. A  
deficiency in butyrate production or sensing in 
IBD leads to increased HDAC activity, repressing 
the expression of anti-inflammatory genes and 
genes involved in epithelial barrier integrity. This 
links the environmental factor (microbiome) 
directly to epigenetic dysregulation (Li et al., 
2025) 
 
ncRNAs: miR-21 is upregulated in IBD                 
mucosa and promotes intestinal inflammation          
by targeting PDCD4, a suppressor of                
IL-10 expression. miR-29 is also             
overexpressed and targets key molecules 
essential for intestinal barrier function. The let-7 
family miRNAs are involved in regulating             
IL-13-mediated inflammation (Goodarzi et al., 
2025). 
 

4. ENVIRONMENTAL TRIGGERS AND 
EPIGENETIC MODIFICATION 

 

The compelling evidence for epigenetic 
dysregulation in immune-mediated diseases 
raises a critical question: what initiates                     
these changes? Environmental factors are the 
primary architects, acting upon a genetically 
susceptible background to instigate pathogenic 
epigenetic reprogramming. These exposures            
can induce stable alterations to the epigenome   
of immune cells and tissue-resident cells, 
effectively "embedding" the memory of a 
environmental insult and lowering the                 
threshold for autoimmune activation. The                 
timing of exposure (e.g., in utero, during 
adolescence) can be as critical as the exposure 
itself due to periods of heightened epigenetic 
plasticity. 

4.1 Tobacco Smoke 
 

Cigarette smoke is one of the most well-
established environmental risk factors for RA and 
other IMIDs. It is a complex mixture of over 7,000 
chemicals, many of which have demonstrable 
epigenetic effects. 
 

Mechanism: Chemicals like benzene and 
hydroquinone can directly inhibit the activity of 
DNMTs by forming covalent adducts or by 
generating reactive oxygen species (ROS) that 
interfere with enzymatic function. This leads to 
DNA hypomethylation. 
 

Evidence: Smokers exhibit global DNA 
hypomethylation in peripheral blood mononuclear 
cells (PBMCs). More specifically, smoking has 
been linked to hypomethylation of the AHRR 
(aryl hydrocarbon receptor repressor) gene and 
site-specific hypomethylation at the CXCL12 
(involved in RA pathogenesis) and IL6 promoters 
in immune cells, promoting a pro-inflammatory 
state (Lim & Kim, 2024; Svendsen et al., 2025). 
This effect can persist for years after smoking 
cessation, illustrating the long-lasting impact of 
epigenetic modification. 
 

4.2 Microbial Infections (e.g., Epstein-
Barr Virus) 

 

Infections, particularly with the Epstein-Barr virus 
(EBV), are strongly associated with an increased 
risk of SLE, MS, and other autoimmune 
conditions. 
 

Mechanism: EBV infection induces widespread 
epigenetic changes in host B cells to facilitate its 
own latency and proliferation. The viral protein 
EBNA2 acts as a transcriptional    regulator that 
binds to numerous autoimmune risk loci 



 
 
 
 

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identified by GWAS, altering their expression and 
histone modification landscape. Furthermore, 
EBV-encoded latent membrane protein 1 (LMP1) 
can dysregulate DNMT expression, leading to 
hypomethylation and activation of endogenous 
retroviruses and autoimmune-related genes 
(Viel, 2024; Zhao et al., 2024)) 
 

Evidence: Patients with SLE have been shown 
to have aberrant hypomethylation of EBV genes, 
leading to loss of viral control and a higher viral 
load. The cross-reactivity between EBV antigens 
(e.g., EBNA1) and self-antigens (e.g., Sm in 
SLE) in an epigenetically permissive environment 
may break tolerance. 
 

4.3 Diet and the Gut Microbiome 
 

Dietary components and the metabolites 
produced by the commensal gut microbiota     
are potent epigenetic modifiers that directly 
influence immune cell function and mucosal 
integrity. 
 

Mechanism: 
 

Methyl donors: Nutrients involved in one-carbon 
metabolism, such as folate, vitamin B12, and 
choline are essential for generating S-
adenosylmethionine (SAM), the universal methyl 
donor for DNA and histone methylation. 
Deficiencies in these nutrients can lead to global 
hypomethylation. 
 

Short-Chain Fatty Acids (SCFAs): Butyrate, 
propionate, and acetate are produced by 
bacterial fermentation of dietary fiber. Butyrate is 
a potent inhibitor of HDAC (particularly Class I 
and IIa). HDAC inhibition in immune cells, 
particularly in the gut, promotes the development 
and function of regulatory T cells (Tregs) via 
hyperacetylation of the Foxp3 promoter and 
other loci, thereby enforcing immune tolerance 
(Xu et al., 2025) 
 

Evidence: A "Western diet" low in fiber reduces 
SCFA production, leading to decreased HDAC 
inhibition, impaired Treg function, and a 
heightened inflammatory state. Butyrate 
supplementation has been shown to ameliorate 
disease in animal models of colitis and MS (Fisse 
et al., 2024). 
 

4.4 Ultraviolet (UV) Radiation 
 

UV radiation is a known trigger for SLE flares 
and skin manifestations. 
Mechanism: UVB exposure can induce DNA 
damage and oxidative stress in keratinocytes, 

leading to the generation of ROS. ROS can 
directly inhibit DNMT1 activity and alter the 
activity of enzymes responsible for histone 
modifications. This can cause demethylation and 
overexpression of genes involved in apoptosis 
and inflammation, such as CD70 and CD154 
(Barnes et al., 2024). 
 

Evidence: UV irradiation of skin cells in culture 
induces demethylation and overexpression of 
autoantigens like Ro/SSA, potentially making 
them more visible to the immune system and 
initiating an autoimmune response. 
 

4.5 Air Pollutants and Chemicals 
 

Particulate matter (PM2.5), organic solvents, and 
other environmental chemicals have been 
implicated in the pathogenesis of IMIDs. 
 

Mechanism: Similar to tobacco smoke, many 
pollutants generate oxidative stress, leading to 
impaired DNMT function and global 
hypomethylation. Some chemicals can also 
directly bind to and activate aryl hydrocarbon 
receptor (AhR), a ligand-activated transcription 
factor that recruits a variety of epigenetic 
modifiers to target genes, influencing Th17/Treg 
balance (Wais and Agrawal, 2024 ; Hahn et al., 
2024). 
 

Evidence: Epidemiological studies link exposure 
to silica dust and organic solvents to an 
increased risk of SLE, RA, and systemic 
sclerosis. Studies show that PM2.5 exposure is 
associated with altered DNA methylation in 
inflammatory genes. 
 

5. TRANSLATIONAL IMPLICATIONS AND 
FUTURE DIRECTIONS 

 

The profound understanding of epigenetic 
dysregulation in immune-mediated diseases is 
rapidly moving from bench to bedside, offering 
unprecedented opportunities for improving 
patient care. The dynamic and reversible nature 
of epigenetic marks positions them as ideal 
targets for novel diagnostic strategies and 
therapeutic interventions, heralding a new era of 
precision medicine in autoimmunity. 
 

5.1 Epigenetic Biomarkers 
 

The quest for specific, sensitive, and non-
invasive biomarkers is central to improving 
outcomes in IMIDs. Epigenetic marks, stable in 
biofluids and reflective of dynamic disease 
activity, hold immense promise. 



 
 
 
 

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237 

 

Table 2. Epigenetic and miRNA biomarkers for diagnosis, monitoring, prognosis, and 
treatment response in SLE and RA 

 

Application Example Potential utility 

Diagnosis Specific miRNA panel (e.g., miR-146a, 
miR-155) in serum for SLE 

Earlier and more accurate diagnosis, 
especially in seronegative patients 

Disease 
Monitoring 

Global DNA methylation levels in PBMCs 
in SLE; CXCL12 methylation in RA 

Objective measure of disease activity; 
predict flare-ups 

Prognosis Methylation status of apoptosis-related 
genes in RA-FLS 

Predict severity of joint destruction and 
disease course 

Treatment 
Response 

Pre-treatment miR-125b levels Predict response to Rituximab in RA or 
SLE 

 
Diagnosis and differential diagnosis: DNA 
methylation signatures and circulating miRNA 
profiles can distinguish patients with a                   
specific IMID from healthy controls and, crucially, 
from those with other clinically similar               
conditions. For instance, a specific methylation 
signature in synovial tissue or peripheral                   
blood can differentiate rheumatoid arthritis                     
from other forms of inflammatory arthritis                    
(e.g., psoriatic arthritis) with higher accuracy     
than current serological tests (Proaño et al., 
2025) 
 

Monitoring disease activity and predicting 
flares: Unlike static genetic risk alleles, 
epigenetic marks change with disease state. 
Serial analysis of circulating cell-free DNA 
(cfDNA) methylation patterns or miRNA levels in 
serum can provide a real-time "epigenetic 
snapshot" of disease activity, potentially 
predicting impending flares before clinical 
symptoms manifest. This allows for pre-emptive 
treatment adjustments (Liu et al., 2024). 
 

Prognosis and Treatment Response: Epigenetic 
profiles may predict disease aggressiveness                
and likelihood of developing extra-articular 
manifestations. Furthermore, baseline epigenetic 
markers could forecast response to specific 
therapies (e.g., predicting non-response to TNF 
inhibitors), enabling a more personalized and 
efficient treatment approach from the outset 
(Shaikh et al., 2024). 
 

5.2 Epigenetic Therapy 
 

The concept of pharmacologically reversing 
aberrant epigenetic marks to restore normal 
gene expression is a groundbreaking therapeutic 
strategy. While most epigenetic drugs are 
currently used in oncology, their repurposing for 
autoimmunity is actively being explored. 
 

DNMT Inhibitors (DNMTi): Drugs like 
azacitidine and decitabine are approved for 

myelodysplastic syndromes. Their use in 
autoimmunity is paradoxical; while they can 
reverse pathological hypermethylation of 
silenced genes, their primary effect is global 
hypomethylation, which could theoretically 
exacerbate diseases like SLE. The future lies in 
developing targeted delivery systems (e.g., 
antibody-drug conjugates) to specific cell types 
or employing low-dose regimens to achieve 
gene-specific rather than global effects (Wen et 
al., 2025). 
 

HDAC Inhibitors (HDACi): This class has 
shown greater immediate promise. Pan-HDAC 
inhibitors like vorinostat and givinostat have 
demonstrated efficacy in preclinical models of 
RA, SLE, and MS by suppressing pro-
inflammatory cytokine production and promoting 
Treg function. More selective HDAC inhibitors 
(e.g., targeting HDAC6, HDAC11) are in 
development to enhance efficacy and reduce off-
target effects (. Notably, the SCFA butyrate is a 
natural HDACi, providing a strong rationale for 
dietary and microbiome-based interventions (Yue 
et al., 2025). 
 

Bromodomain and Extra-Terminal (BET) 
inhibitors: These compounds disrupt the 
reading of histone acetylation marks by BET 
proteins. They have potent anti-inflammatory 
effects by downregulating key inflammatory 
genes (e.g., NFKB, IL6) and have shown efficacy 
in multiple animal models of IMIDs (Khokhar et 
al., 2024). 
 

miRNA-based therapeutics: This approach 
offers exquisite specificity. Mimics (to restore 
levels of deficient miRNAs like miR-146a) and 
antagomirs or locked nucleic acids (LNAs) (to 
silence overexpressed miRNAs like miR-155) are 
in various stages of preclinical and early clinical 
development. The major challenge remains the 
efficient and targeted delivery of these 
oligonucleotides to relevant immune cells in vivo 
(Bannazadeh Baghi et al., 2024). 



 
 
 
 

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238 

 

6. CONCLUSION 
 
The investigation into epigenetic dysregulation 
has fundamentally reshaped our understanding 
of immune-mediated diseases. No longer viewed 
as disorders governed solely by a deterministic 
genetic code, IMIDs are now recognized as 
conditions where dynamic epigenetic 
mechanisms interpret genetic susceptibility 
through the lens of environmental exposure. This 
review has synthesized compelling evidence that 
establishes aberrant DNA methylation, histone 
modifications, and non-coding RNA expression 
not as mere epiphenomena, but as central 
drivers of pathogenesis. These mechanisms 
directly mediate the loss of immune tolerance, 
hyperactivation of inflammatory pathways, and 
tissue damage characteristic of diseases like 
SLE, RA, MS, and IBD. 
 
The environmental dimension is particularly 
pivotal, with factors such as tobacco smoke, viral 
infections (notably EBV), diet, and the gut 
microbiome acting as powerful epigenetic 
modifiers. These triggers can induce stable, 
heritable changes in gene expression that lower 
the threshold for autoimmunity, effectively 
encoding the memory of environmental insults 
within the immune system and explaining the 
notable discordance in genetically identical twins. 
 
This profound mechanistic insight unlocks 
immense translational potential. The dynamic 
nature of the epigenome offers a unique 
opportunity to develop novel epigenetic 
biomarkers for early diagnosis, precise 
prognosis, and real-time monitoring of disease 
activity, moving beyond the limitations of current 
serological and clinical markers. Furthermore, 
the reversibility of epigenetic marks paves the 
way for a revolutionary therapeutic strategy: 
epigenetic therapy. The repurposing and 
refinement of drugs targeting DNMTs, HDACs, 
BET proteins, and specific miRNAs hold the 
promise of not just suppressing inflammation but 
potentially restoring immunological balance and 
inducing long-term remission by reversing the 
root epigenetic dysfunction. 
 
However, the path forward is not without 
challenges. The field must overcome hurdles 
related to the cell-type specificity of interventions, 
the complex crosstalk within the epigenome, and 
the long-term safety of modulating these 
fundamental regulatory systems. Future research 
must focus on large-scale integrative multi-omics 
studies to validate biomarkers and on developing 

novel targeted delivery systems to enhance the 
precision of epigenetic drugs. 
 
In conclusion, the study of epigenetics has 
provided the missing link between genes and 
environment in immune-mediated diseases. It 
offers a more complete and nuanced disease 
model and, most importantly, illuminates a 
promising path toward personalized medicine. By 
reading and rewriting the epigenetic code that 
goes awry in autoimmunity, we are poised to 
develop more effective strategies for prediction, 
prevention, and treatment, ultimately aiming to 
restore the delicate balance of the immune 
system and improve the lives of millions of 
patients worldwide. 
 

CONSENT 
 
It is not applicable. 
 

ETHICAL APPROVAL 
 

It is not applicable. 
 

DISCLAIMER (ARTIFICIAL INTELLIGENCE) 
 
Author(s) hereby declare that NO generative AI 
technologies such as Large Language Models 
(ChatGPT, COPILOT, etc.) and text-to-image 
generators have been used during the writing or 
editing of this manuscript.  
 

COMPETING INTERESTS 
 
Authors have declared that no competing 
interests exist. 
 

REFERENCES 
 
Antonazzo, G., Gaudet, P., Lovering, R. C., & 

Attrill, H. (2024). Representation of non-
coding RNA-mediated regulation of gene 
expression using the Gene Ontology. RNA 
Biology, 21(1), 981–993. 

Araki, Y., & Mimura, T. (2024). Epigenetic 
dysregulation in the pathogenesis of 
systemic lupus erythematosus. 
International Journal of Molecular 
Sciences, 25(2), 1019. 

Arneth, B. (2024). Genes, gene loci, and their 
impacts on the immune system in the 
development of multiple sclerosis: A 
systematic review. International Journal of 
Molecular Sciences, 25(23), 12906. 

Ates, I., Terzi, U., Suzen, S., & Irham, L. M. 
(2025). An overview on Sjögren’s 



 
 
 
 

Ajibola and Ayodele; Asian J. Immunol., vol. 8, no. 1, pp. 230-241, 2025; Article no.AJI.144830 
 
 

 
239 

 

syndrome and systemic lupus 
erythematosus’ genetics. Toxicology 
Research, 14(1), tfae194. 

Ausserwinkler, M., Gensluckner, S., Voelkerer, 
A., Thiel, J., Neumann, H. J., Flamm, M., 
... & Wernly, B. (2025). Genetic 
relationship between rheumatoid arthritis 
and cardiovascular diseases: A systematic 
review of Mendelian randomization 
studies. Wiener klinische Wochenschrift, 
137(9), 272–278. 

Bannazadeh Baghi, H., Bayat, M., Mehrasa, P., 
Alavi, S. M. A., Lotfalizadeh, M. H., Memar, 
M. Y., ... & Mirzaei, H. (2024). Regulatory 
role of microRNAs in virus-mediated 
inflammation. Journal of Inflammation, 
21(1), 43. 

Barnes, B. M., Shyne, A., Gunn, D. A., Griffiths, 
C. E., & Watson, R. E. (2024). Epigenetics 
and ultraviolet radiation: Implications for 
skin ageing and carcinogenesis. Skin 
Health and Disease, 4(6), e410. 

Chen, G., Zhang, L., Wang, R., & Xie, Z. (2024). 
Histone methylation in Epstein–Barr virus-
associated diseases. Epigenomics, 16(11–
12), 865–877. 

Chen, Y., Guo, P., & Dong, Z. (2024). The role of 
histone acetylation in transcriptional 
regulation and seed development. Plant 
Physiology, 194(4), 1962–1979. 

Deng, T., Wang, Z., Geng, Q., Wang, Z., Jiao, Y., 
Diao, W., & Xiao, C. (2024). Methylation of 
T and B lymphocytes in autoimmune 
rheumatic diseases. Clinical Reviews in 
Allergy & Immunology, 66(3), 401–422. 

Elbahrawi, R., Aljoudi, S., Rabeh, N., Dimassi, 
Z., Alhosani, K. M., & Hamdan, H. (2024). 
Epigenetics: Implication on multiple 
sclerosis. In Exploring the Effects of                  
Diet on the Development and Prognosis                   
of Multiple Sclerosis (MS) (pp. 207–                  
218). Singapore: Springer Nature 
Singapore. 

Enayati, S., Moharamoghli, M., Farazmand, A., 
Hassan-Zadeh, V., Poursani, S., 
Madreseh, E., ... & Mahmoudi, M. (2024). 
Upregulated gene expression of histone 
deacetylases (HDAC) 1, 2, and 11 in 
peripheral blood mononuclear cells of 
rheumatoid arthritis patients. Journal of 
Cellular Immunology, 6(4), 188–195. 

Fisse, A. L., Motte, J., Kalliopi, A. P. D., & 
Pitarokoili, M. D. (2024). Influence of                 
the short-chain fatty acid propionic acid             
on the peripheral immune regulation in             
the context of chronic inflammatory 
demyelinating polyneuropathy (CIDP). 

Gibson, F., Hanly, A., Grbic, N., Grunberg, N., 
Wu, M., Collard, M., & Alani, R. M. (2022). 
Epigenetic dysregulation in autoimmune 
and inflammatory skin diseases. Clinical 
Reviews in Allergy & Immunology, 63(3), 
447–471. 
https://link.springer.com/article/10.1007/s1
2016-022-08956-8 

Goodarzi, G., Tehrani, S. S., Fana, S. E., 
Saleknezhad, N., Panahi, G., Rayatpisheh, 
M., & Anushiravani, A. (2025). Evaluation 
of microRNA-29a expression and 
dipeptidyl-peptidase 4 level in ulcerative 
colitis patients. Acta Biochimica Iranica. 

Hahn, J., Ding, S., Im, J., Harimoto, T., Leong, K. 
W., & Danino, T. (2024). Bacterial 
therapies at the interface of synthetic 
biology and nanomedicine. Nature 
Reviews Bioengineering, 2(2), 120–135. 

Harris, J., Mayran, A., Gouhier, A., Gauthier, Y., 
Sleiman, N. H., Merabet, S., ... & Drouin, J. 
(2025). Dual DNA demethylation 
mechanisms implement epigenetic 
memory driven by the pioneer factor PAX7. 
Science Advances, 11(20), eadu6632. 

Jay, A., Pondevida, C. M., & Vahedi, G. (2025). 
The epigenetic landscape of fate decisions 
in T cells. Nature Immunology, 1–13. 

Kaszycki, J., & Kim, M. (2025). Epigenetic 
regulation of transcription factors involved 
in NLRP3 inflammasome and NF-κB 
signaling pathways. Frontiers in 
Immunology, 16, 1529756. 

Khan, A., Mazumder, A., Pentela, B., Mishra, R., 
& Singh, S. K. (2024). The ability of 
indigenous plants in alleviating rheumatoid 
arthritis: A comprehensive review. Current 
Rheumatology Reviews. 

Khokhar, M., Dey, S., Tomo, S., Jaremko, M., 
Emwas, A. H., & Pandey, R. K. (2024). 
Unveiling novel drug targets and emerging 
therapies for rheumatoid arthritis: A 
comprehensive review. ACS 
Pharmacology & Translational Science, 
7(6), 1664–1693. 

Kong, J., Lyu, H., Ouyang, Q., Shi, H., Zhang, R., 
Xiao, S., ... & Tang, J. (2024). Insights into 
the roles of epigenetic modifications in 
ferroptosis. Biology, 13(2), 122. 

Kwon, G., Park, Y., Kang, K., & Kang, K. (2024). 
Selective epigenetic regulation of IFN-γ 
signature genes by JAK inhibitor in 
inflammatory diseases. bioRxiv, 2024–08. 

Li, C., Gu, S., Zhang, Y., Zhang, Z., Wang, J., 
Gao, T., ... & Chen, Y. (2025). Histone 
deacetylase in inflammatory bowel 
disease: Novel insights. Therapeutic 

https://link.springer.com/article/10.1007/s12016-022-08956-8
https://link.springer.com/article/10.1007/s12016-022-08956-8


 
 
 
 

Ajibola and Ayodele; Asian J. Immunol., vol. 8, no. 1, pp. 230-241, 2025; Article no.AJI.144830 
 
 

 
240 

 

Advances in Gastroenterology, 18, 
17562848251318833. 

Lim, E. Y., & Kim, G. D. (2024). Particulate 
matter-induced emerging health effects 
associated with oxidative stress                        
and inflammation. Antioxidants, 13(10), 
1256. 

Lin, H. Y., Lee, C. L., Tu, Y. R., Chang, Y. H., 
Niu, D. M., Chang, C. Y., ... & Lin, S. P. 
(2024). Quantitative DNA methylation 
analysis and epigenotype-phenotype 
correlations in Taiwanese patients with 
Silver–Russell syndrome. International 
Journal of Medical Sciences, 21(1), 8. 

Liu, X., Zhou, S., Huang, M., Zhao, M., Zhang, 
W., Liu, Q., ... & Chen, X. (2024). DNA 
methylation and whole-genome 
transcription analysis in CD4+ T cells from 
systemic lupus erythematosus patients 
with or without renal damage. Clinical 
Epigenetics, 16(1), 98. 

Mahurkar‐Joshi, S., Thompson, M., Villarruel, E., 
Lewis, J. D., Lin, L. D., Farid, M., ... & 
Chang, L. (2025). Genome‐wide DNA 
methylation identifies potential 
disease‐specific biomarkers and 
pathophysiologic mechanisms in irritable 
bowel syndrome, inflammatory bowel 
disease, and celiac disease. 
Neurogastroenterology & Motility, 37(2), 
e14980. 

Mehta, P., & Mazumder, S. (2025). miR-146a is 
critical for orchestrating Mycobacterium 
fortuitum survival through anti-
inflammatory and M2 macrophage 
responses in fish. Fish & Shellfish 
Immunology, 161, 110271. 

Nie, Y., Song, C., Huang, H., Mao, S., Ding, K., & 
Tang, H. (2024). Chromatin modifiers in 
human disease: From functional roles to 
regulatory mechanisms. Molecular 
Biomedicine, 5(1), 12. 

Prideaux, E. B., Boyle, D. L., Choi, E., Buckner, 
J. H., Robinson, W. H., Holers, V. M., ... & 
Wang, W. (2024). Epigenetic trajectory 
predicts development of clinical 
rheumatoid arthritis in ACPA+ individuals: 
Targeting Immune Responses for 
Prevention of Rheumatoid Arthritis (TIP-
RA). bioRxiv, 2024-10. 

Proaño, A., Sarrion-Perez, G., Bagan, L., & 
Bagan, J. (2025). Genome-wide DNA 
methylation confirms oral squamous cell 
carcinomas in proliferative verrucous 
leukoplakia as a distinct oral cancer 
subtype: A case–control study. Cancers, 
17(2), 245. 

Ribeiro, A. A., Carvalho, L. M., da Mota, J. C., 
Nonino, C. B., Gualano, B., Nunes, J. A., 
... & Nicoletti, C. F. (2024). Diet, DNA 
methylation, and systemic lupus 
erythematosus: Evidence and perspectives 
focused on personalized nutrition. Lifestyle 
Genomics, 17(1), 31–40. 

Roy, S., Shanmugam, G., Pradeep, R., George, 
M., & Sarkar, K. (2025). Epigenetic control 
of T helper cells differentiation: A 
mechanistic insight into the association 
between acute leukemia and coronary 
artery disease. Medical Oncology, 42(7), 
272. 

Royo, M., Joseph-Mullol, B., Sandoval, S., 
Moline, T., Sole, C., & Cortes-Hernandez, 
J. (2025). Integrative miRNA-mRNA 
profiling uncovers mechanisms of 
belimumab action in systemic lupus 
erythematosus. Frontiers in Immunology, 
16, 1553971. 

Sarre, L. A., Gastellou Peralta, G. A., Romero 
Charria, P., Ovchinnikov, V., & de 
Mendoza, A. (2025). Repressive cytosine 
methylation is a marker of viral gene 
transfer across divergent eukaryotes. 
Molecular Biology and Evolution, 42(8), 
msaf176. 

Seyedi, D., Espandar, N., Hojatizadeh, M., 
Mohammadi, Y., Sadri, F., & Rezaei, Z. 
(2024). Noncoding RNAs in rheumatoid 
arthritis: Modulators of the NF-κB signaling 
pathway and therapeutic implications. 
Frontiers in Immunology, 15, 1486476. 

Shaheen, N., Shaheen, A., Osama, M., 
Nashwan, A. J., Bharmauria, V., & Flouty, 
O. (2024). MicroRNAs regulation in 
Parkinson’s disease, and their potential 
role as diagnostic and therapeutic targets. 
npj Parkinson's Disease, 10(1), 186. 

Shaikh, F. S., Siegel, R. J., Srivastava, A., Fox, 
D. A., & Ahmed, S. (2024). Challenges and 
promise of targeting miRNA in rheumatic 
diseases: A computational approach to 
identify miRNA association with cell types, 
cytokines, and disease mechanisms. 
Frontiers in Immunology, 14, 1322806. 

Smith, Z. D., Hetzel, S., & Meissner, A. (2025). 
DNA methylation in mammalian 
development and disease. Nature Reviews 
Genetics, 26(1), 7–30. 

Somers, E. C., Goodrich, J. M., Wang, L., 
Harlow, S. D., Marder, W., Hassett, A. L., 
Zick, S. M., et al. (2024). Associations 
between CD70 methylation of T cell DNA 
and age in adults with systemic lupus 
erythematosus and population controls: 



 
 
 
 

Ajibola and Ayodele; Asian J. Immunol., vol. 8, no. 1, pp. 230-241, 2025; Article no.AJI.144830 
 
 

 
241 

 

The Michigan Lupus Epidemiology & 
Surveillance (MILES) Program. Journal of 
Autoimmunity, 142, 103137. 

Stroeks, S. L., Henkens, M. T., Dominguez, F., 
Merlo, M., Hellebrekers, D. M., Gonzalez-
Lopez, E., ... & Verdonschot, J. A. (2025). 
Genetic landscape of patients with dilated 
cardiomyopathy and a systemic immune-
mediated disease. Heart Failure, 13(1), 
133–145. 

Svendsen, A. J., Mengel-From, J., Junker, P., 
Dalgård, C., Davey Smith, G., Relton, C. 
L., ... & Tan, Q. (2025). Differential DNA 
methylation patterns in whole blood from 
ACPA-positive patients with DMARD naïve 
rheumatoid arthritis at clinical disease 
onset. Frontiers in Immunology, 16, 
1488161. 

Ueberheide, B. M., Mollah, S., & Garcia, B. A. 
(2024). On the hunt for the histone                 
code. Molecular & Cellular Proteomics, 
23(12). 

Viel, K. C. M. F. (2024). Epstein-Barr Nuclear 
Antigen 2 (EBNA2) Type 2: Mechanisms 
and disease implications (Doctoral 
dissertation, University of Cincinnati). 

Wais, N., & Agrawal, D. K. (2024). Systemic 
lupus erythematosus: Gene 
polymorphisms, epigenetics, 
environmental, hormonal and nutritional 
factors in the consideration of personalized 
therapy. Archives of Internal Medicine 
Research, 7(4), 331. 

Wen, J., Liu, J., Wan, L., Sun, Y., & Wang, F. 
(2025). Crosstalk between N6-
methyladenosine modification and ncRNAs 
in rheumatic diseases: Therapeutic and 

diagnostic implications. Inflammation 
Research, 74(1), 79. 

Wilkinson, M. J., & Shapiro, M. D. (2024). 
Immune-mediated inflammatory diseases, 
dyslipidemia, and cardiovascular risk: A 
complex interplay. Arteriosclerosis, 
Thrombosis, and Vascular Biology, 44(12), 
2396–2406. 

Xie, J., Che, S., Liu, J., & Long, X. (2025). 
SIRT1: Potential target in glucocorticoid-
resistant diseases. Frontiers in 
Immunology, 16, 1514745. 

Xu, X., Zhou, J., Xie, H., Zhang, R., Gu, B., Liu, 
L., ... & Chang, X. (2025). 
Immunomodulatory mechanisms of the gut 
microbiota and metabolites on regulatory T 
cells in rheumatoid arthritis. Frontiers in 
Immunology, 16, 1610254. 

Yue, S., Fan, J., Xie, D., Cao, C., Wang, Z., 
Huang, J., ... & Liang, C. (2025). Unveiling 
the therapeutic potential: Targeting 
fibroblast-like synoviocytes in rheumatoid 
arthritis. Expert Reviews in Molecular 
Medicine, 1–24. 

Zhang, Y., Maskan Bermudez, N., Sa, B., 
Maderal, A. D., & Jimenez, J. J. (2024). 
Epigenetic mechanisms driving the 
pathogenesis of systemic lupus 
erythematosus, systemic sclerosis and 
dermatomyositis. Experimental 
Dermatology, 33(1), e14986. 

Zhao, Y., Zhang, Q., Zhang, B., Dai, Y., Gao, Y., 
Li, C., ... & Li, C. (2024). Epstein–Barr 
viruses: Their immune evasion strategies 
and implications for autoimmune diseases. 
International Journal of Molecular 
Sciences, 25(15), 8160. 

 
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