Investigation of methylation status of interleukin-16 and autoimmune regulator gene promoter regions in Behçet's disease
Melih Akpunar1
, Demet Yalcin Kehribar2, Serkan Günaydın3, Hilal Koyuncu4, Zülfinaz Betül Celik5, Metin Özgen1
1Department of Internal Medicine, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye
2Department of Internal Medicine, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye
3Department of Rheumatology, Ministry of Health Ordu Training and Research Hospital, Ordu, Türkiye
4Department of Medical Biology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye
5Department of Medical Biology, Samsun University, Samsun, Türkiye
Keywords: Autoimmune regulator gene, Behçet’s disease, interleukin-16.
Abstract
Objectives: The aim of this study was to determine the epigenetic changes in interleukin-16 (IL-16) and autoimmune regulator (AIRE) genes in Behçet’s disease (BD) and to investigate the relationship between these changes and the disease mechanism.
Patients and methods: Between October 2022 and January 2023, a total of 40 patients (20 males, 20 females; mean age: 37.0±11.4 years; range, 19 to 71 years) who met the 2014 International Criteria for Behçet’s Disease with no concomitant diseases and who were either newly diagnosed or under follow-up and 40 age- and sex-matched healthy hospital staff as the control group (20 males, 20 females mean age: 35.1±5.7 years; range, 29 to 45 years) with no chronic diseases or active infections were included. Peripheral blood samples were obtained from all participants, and genomic deoxyribonucleic acid (DNA) was isolated. The DNA samples were modified using a bisulfite modification kit. Subsequently, the promoter methylation profiles of IL-16 and AIRE genes were determined using methylation-specific polymerase chain reaction (MSP) with primers specifically designed for methylation.
Results: In both BD and control groups, methylation was detected in the promoter region of IL-16, indicating a weak expression of the IL-16 gene. In contrast, while the promoter region of the AIRE gene was methylated in all control participants, it was unmethylated in all patients with BD.
Conclusion: This is the first study to evaluate the methylation status of both AIRE and IL-16 genes in BD. Our study results suggest that the promoter region of the AIRE gene is unmethylated in BD and that AIRE gene is activated in BD and produces autoimmune regulatory proteins that eliminate autoreactive T cells, suggesting a tendency toward autoimmunity in BD. These findings also suggest that IL-16, which is involved in the pathogenesis of many rheumatic diseases, does not play a significant role in the pathogenesis of BD.
Citation: Akpunar M, Yalcin Kehribar D, Günaydın S, Koyuncu H, Celik ZB, Özgen M. Investigation of methylation status of interleukin-16 and autoimmune regulator gene promoter regions in Behçet's disease. Arch Rheumatol 2025;40(1):80- 86. doi: 10.46497/ArchRheumatol.2025.11022.
Idea/concept: Z.B.Ç.; Design, control/supervision: D.Y.K.; Data collection and/or processing: M.A.; Analysis and/or interpretation: D.Y.K., M.Ö., S.G.; Literature review, writing the article: M.A., D.Y.K., M.Ö.; Critical review: H.K., M.A., D.Y.K., S.G., M.Ö., Z.B.Ç.; References and fundings: Materials: Hilal Koyuncu, M.A., D.Y.K.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
Funding: This research was financially supported by the Ondokuz Mayıs University Scientific Research Projects Unit (Project no: B.30.2.ODM.20.08/859-600).
The data that support the findings of this study are available from the corresponding author upon reasonable request.