Skip to main content

Autoimmune Rheumatic Diseases

Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases


Objective


To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features.

Methods


Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC).

Results


Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher methylation than HC and AS (p < 0.01) but lower than SLE (p < 0.05). SLE patients showed higher methylation compared to HC, AS, and PsA (p < 0.001, 0.01, and 0.05, respectively). No significant differences were found in patients with SS compared to other autoimmune diseases and HC. Methylation at cg19599951_103 (r = 0.17, p < 0.05) and cg19599951_209 (r = 0.22, p < 0.01), along with the CC haplotype (r = 0.21, p < 0.01), showed significant positive correlations with erythrocyte sedimentation rate (ESR), while the CT (r = −0.27, p < 0.001) and TT haplotypes (r = −0.19, p < 0.05) were negatively correlated. For C-reactive protein (CRP), methylation at cg19599951_103 (r = 0.29, p < 0.001) and cg19599951_209 (r = 0.33, p < 0.0001), and the CC haplotype (r = 0.34, p < 0.0001) was positively correlated, whereas the CT (r = −0.36, p < 0.0001) and TT (r = −0.30, p < 0.0001) haplotypes were negatively correlated. Significant negative correlations were observed between the CT haplotype and rheumatoid factor (r = −0.25, p < 0.01), and anti-citrullinated protein antibody (r = −0.20, p < 0.05). No significant correlations were found in patients with SLE, AS, and SS. Receiver operating characteristic analysis showed CXCR5 methylation could classify patients with RA versus those with AS (AUC: 0.624−0.967).

Conclusion


Differential circulating CXCR5 methylation levels were observed in autoimmune rheumatic diseases, which correlated with inflammatory mediators in RA and may serve as potential biomarkers for RA diagnosis.

Our findings revealed significant differences in CXCR5 circulating methylation levels between patients with RA and those with SLE relative to healthy individuals, and notable differences between patients with RA and those with AS and SLE. CXCR5 methylation levels were able to distinctly differentiate patients with CCP-negative RA from those with AS. Additionally, CXCR5 methylation levels in patients with RA were significantly correlated with inflammatory markers. 

The results further substantiated that alterations in CXCR5 methylation have a role in the pathogenesis of autoimmune illnesses and could potentially serve as markers reflecting the inflammatory levels in RA, assisting disease diagnosis. The underlying mechanisms behind these differential methylation patterns warrant further investigation, especially in terms of how CXCR5 methylation specifically influences immune function and disease progression. Subsequent studies may also explore the methylation status of additional inflammation signaling pathways related to ARDs, to clarify the epigenetic regulatory landscape shaping these pathologies.

rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögren's syndrome, polymyositis, dermatomyositis, ankylosing spondylitis, psoriatic arthritis, vasculitis, antiphospholipid syndrome, connective tissue disease, autoantibodies, chronic inflammation, immune dysregulation, joint pain, fatigue, immunosuppressive therapy, biologics, cytokines

#AutoimmuneDiseases, #RheumaticDiseases, #LupusAwareness, #RheumatoidArthritis, #SclerodermaWarrior, #SjogrensSyndrome, #VasculitisAwareness, #PsoriaticArthritis, #ChronicIllness, #Inflammation, #Autoimmunity, #JointPain, #ImmuneSystem, #BiologicTherapy, #ConnectiveTissueDisease, #Fatigue, #Autoantibodies, #ImmuneHealth, #ArthritisSupport, #RAAwareness


International Conference on Genetics and Genomics of Diseases

Visit: genetics-conferences.healthcarek.com

Award Nomination: genetics-conferences.healthcarek.com/award-nomination/?ecategory=Awards&rcategory=Awardee

Award registration: genetics-conferences.healthcarek.com/award-registration/

For Enquiries: contact@healthcarek.com

Get Connected Here
---------------------------------
---------------------------------
in.pinterest.com/Dorita0211
twitter.com/Dorita_02_11_
facebook.com/profile.php?id=61555903296992
instagram.com/p/C4ukfcOsK36
genetics-awards.blogspot.com/
youtube.com/@GeneticsHealthcare

Comments

Popular posts from this blog

Fruitful innovation

Fruitful innovation: Transforming watermelon genetics with advanced base editors The development of new adenine base editors (ABE) and adenine-to-thymine/ guanine base editors (AKBE) is transforming watermelon genetic engineering. These innovative tools enable precise A:T-to-G and A:T-to-T base substitutions, allowing for targeted genetic modifications. The research highlights the efficiency of these editors in generating specific mutations, such as a flowerless phenotype in ClFT (Y84H) mutant plants. This advancement not only enhances the understanding of gene function but also significantly improves molecular breeding, paving the way for more efficient watermelon crop improvement. Traditional breeding methods for watermelon often face challenges in achieving desired genetic traits efficiently and accurately. While CRISPR/Cas9 has provided a powerful tool for genome editing, its precision and scope are sometimes limited. These limitations highlight the need for more advanced gene-e...

Genetic factors with clinical trial stoppage

Genetic factors associated with reasons for clinical trial stoppage Many drug discovery projects are started but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the free-text reasons for 28,561 clinical trials that stopped before their endpoints were met. We then evaluated these classes in light of the underlying evidence for the therapeutic hypothesis and target properties. We found that trials are more likely to stop because of a lack of efficacy in the absence of strong genetic evidence from human populations or genetically modified animal models. Furthermore, certain trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is broadly expressed across tissues. These results support the growing use of human genetics to ...

Genetics study on COVID-19

Large genetic study on severe COVID-19 Bonn researchers confirm three other genes for increased risk in addition to the known TLR7 gene Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in cooperation with other research teams from Germany, the Netherlands, Spain and Italy, investigated a particularly large group of affected individuals. They confirmed the central and already known role of the TLR7 gene in severe courses of the disease in men, but were also able to find evidence for a contribution of the gene in women. In addition, they were able to show that genetic changes in three other genes of the innate immune system contribute to severe COVID-19. The results have now been published in the journal " Human Genetics and Genomics Advances ". Even though the number of severe cases following infection with the SARS-CoV-...