Iranian Journal of Immunology

Hypomethylation of OAS2 and OAS3 Gene Promoters: Insights into the ‎Pathogenesis of Systemic Lupus Erythematosus

Document Type : Original Article

Authors

Esmat Rigi Yousefabadi 1
Zahra Ourang 2, 3
Farhad Gharibdoost 2
Seyedeh Tahereh Faezi 2
Mohammad Saatchi 4
Delnya Gholami 1
Emran Esmaeilzadeh 5
Hamid Reza Khorram Khorshid 6

1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

2 Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Internal Medicine, Arak University of Medical Sciences, Arak, Iran.

4 Department of Biostatistics and Epidemiology, University of Social Welfare and Rehabilitation ‎Sciences, Tehran, Iran.

5 ‎Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.

6 Personalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, ‎Tehran, Iran.

https://doi.org/10.22034/iji.2025.105409.2944
Abstract
Background: DNA methylation plays a key role in systemic lupus erythematosus (SLE) by regulating gene expression and impacting immune system functions. In SLE, abnormal DNA methylation patterns can lead to the overexpression of pro-inflammatory genes and downregulation of the regulatory genes, contributing to autoimmunity. This dysregulation can increase susceptibility to  SLE. Understanding these methylation changes could help discover new therapeutic strategies for managing SLE.
Objective: To evaluate methylation levels of OAS2 and OAS3 in peripheral blood mononuclear cells (PBMCs) in volunteers with SLE were evaluated.
Methods: In this case-control study, we collected 207 peripheral blood samples from 102 SLE patients and 105 healthy subjects. After isolating the PBMCs, methylation analysis was performed using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.
Results: The control group had an average OAS2 methylation percentage of 40.02% ± 24.59%, whereas the SLE group had a significantly lower average of 19.46% ± 21.98%. This finding indicates a significant hypomethylation of OAS2 in the SLE cohort (P<0.001). Additionally, a significant difference was observed in the mean methylation levels of OAS3, with SLE patients exhibiting 14.11% ± 19.50% compared to healthy controls at 25.32% ± 20.82% (P<0.001). Patients with renal damage also showed significantly lower OAS2 methylation levels than SLE individuals without renal damage (P<0.001). Furthermore, a negative connection was found between the OAS2 methylation level and creatinine (r= -0.266, P= 0.007).
Conclusion: The pattern of methylation levels observed in OAS2 and OAS3 within PBMCs may provide valuable insights into the mechanisms underlying SLE development.

Keywords

Methylation
OAS2
OAS3
Systemic lupus erythematosus
Iranian Journal of Immunology
Volume 22, Issue 2
Spring 2025
Pages 155-164

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