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image of CD82 Methylation Patterns in Inflammatory Arthritis and their Clinical Association with Hypertension in Rheumatoid Arthritis

Abstract

Objective

This study aimed to compare CD82 methylation patterns in peripheral blood among patients with rheumatoid arthritis [RA], inflammatory arthritis, and healthy controls [HC] and to assess their clinical associations with hypertension in RA.

Methods

In this cross-sectional study, CD82 methylation at positions 44596705-44596865 on chromosome 11 was analyzed using targeted methylation techniques in peripheral blood from patients with RA, psoriatic arthritis [PsA], ankylosing spondylitis [AS], gout, and HC.

Results

CD82 cg22143324 methylation levels were significantly different between RA patients and healthy controls [<0.0001], PsA [=0.0281], and AS [=0.0360]. In RA subgroups, individuals negative for both rheumatoid factor [RF] and cyclic citrullinated peptide [CCP] [RA-DN], as well as those positive for both [RA-DP], exhibited significantly different methylation levels compared to HC [=0.0355 and <0.0001, respectively]. ROC analysis indicated a promising diagnostic potential for CD82 cg22143324 methylation, especially with the TTT haplotype. Correlation analysis revealed significant associations between CD82 methylation and CCP levels, as well as hypertension in RA patients.

Conclusion

The analysis conducted revealed altered CD82 cg22143324 methylation in RA, with potential utility in distinguishing seronegative patients from healthy controls. An association between lower methylation levels and comorbid hypertension in RA patients was also observed, warranting further investigation.

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2025-05-20
2025-09-14

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References

  1. Hammaker D. Firestein G.S. Epigenetics of inflammatory arthritis. Curr. Opin. Rheumatol. 2018 30 2 188 196 10.1097/BOR.0000000000000471 29194108
    [Google Scholar]
  2. Manabe Y. Norikane T. Yamamoto Y. [18F] FDG uptake in patients with spondyloarthritis: correlation with serum inflammatory biomarker levels. EJNMMI Res. 2023 13 1 15 10.1186/s13550‑023‑00964‑9 36792786
    [Google Scholar]
  3. Beringer A. Miossec P. Systemic effects of IL-17 in inflammatory arthritis. Nat. Rev. Rheumatol. 2019 15 8 491 501 10.1038/s41584‑019‑0243‑5 31227819
    [Google Scholar]
  4. Di Matteo A. Bathon J.M. Emery P. Rheumatoid arthritis. Lancet 2023 402 10416 2019 2033 10.1016/S0140‑6736(23)01525‑8 38240831
    [Google Scholar]
  5. England B.R. Thiele G.M. Anderson D.R. Mikuls T.R. Increased cardiovascular risk in rheumatoid arthritis: Mechanisms and implications. BMJ 2018 361 k1036 10.1136/bmj.k1036 29685876
    [Google Scholar]
  6. Verstappen S.M.M. Lunt M. Luben R.N. Demographic and disease-related predictors of abnormal lung function in patients with established inflammatory polyarthritis and a comparison with the general population. Ann. Rheum. Dis. 2013 72 9 1517 1523 10.1136/annrheumdis‑2012‑201698 23065733
    [Google Scholar]
  7. Allis C.D. Jenuwein T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 2016 17 8 487 500 10.1038/nrg.2016.59 27346641
    [Google Scholar]
  8. Ballestar E. Sawalha A.H. Lu Q. Clinical value of DNA methylation markers in autoimmune rheumatic diseases. Nat. Rev. Rheumatol. 2020 16 9 514 524 10.1038/s41584‑020‑0470‑9 32759997
    [Google Scholar]
  9. Querol Cano L. Dunlock V.M.E. Schwerdtfeger F. van Spriel A.B. Membrane organization by tetraspanins and galectins shapes lymphocyte function. Nat. Rev. Immunol. 2024 24 3 193 212 10.1038/s41577‑023‑00935‑0 37758850
    [Google Scholar]
  10. Huang C. Hays F.A. Tomasek J.J. Benyajati S. Zhang X.A. Tetraspanin CD82 interaction with cholesterol promotes extracellular vesicle–mediated release of ezrin to inhibit tumour cell movement. J. Extracell. Vesicles 2020 9 1 1692417 10.1080/20013078.2019.1692417 31807237
    [Google Scholar]
  11. Kim Y.I. Shin M.K. Lee J.W. Chung J.H. Lee M.H. Decreased expression of KAI1/CD82 metastasis suppressor gene is associated with loss of heterozygosity in melanoma cell lines. Oncol. Rep. 2009 21 1 159 164 19082457
    [Google Scholar]
  12. Drucker L. Tohami T. Tartakover-Matalon S. Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines. Carcinogenesis 2006 27 2 197 204 10.1093/carcin/bgi209 16113057
    [Google Scholar]
  13. Neumann E. Schwarz M.C. Hasseli R. Tetraspanin CD82 affects migration, attachment and invasion of rheumatoid arthritis synovial fibroblasts. Ann. Rheum. Dis. 2018 77 11 1619 1626 10.1136/annrheumdis‑2018‑212954 29980577
    [Google Scholar]
  14. Kay J Upchurch KS ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology 2012 51 vi5-9.(Suppl.6) 10.1093/rheumatology/kes279 23221588
    [Google Scholar]
  15. Taylor W. Gladman D. Helliwell P. Marchesoni A. Mease P. Mielants H. Classification criteria for psoriatic arthritis: Development of new criteria from a large international study. Arthritis Rheum. 2006 54 8 2665 2673 10.1002/art.21972 16871531
    [Google Scholar]
  16. Rudwaleit M. van der Heijde D. Landewé R. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): Validation and final selection. Ann. Rheum. Dis. 2009 68 6 777 783 10.1136/ard.2009.108233 19297344
    [Google Scholar]
  17. Neogi T. Jansen T.L.T.A. Dalbeth N. 2015 Gout classification criteria: An american college of rheumatology/european league against rheumatism collaborative initiative. Arthritis Rheumatol. 2015 67 10 2557 2568 10.1002/art.39254 26352873
    [Google Scholar]
  18. Coffey C.M. Crowson C.S. Myasoedova E. Matteson E.L. Davis J.M. Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: Missing the window of opportunity. Mayo Clin. Proc. 2019 94 11 2241 2248 10.1016/j.mayocp.2019.05.023 31619364
    [Google Scholar]
  19. Yeung L. Hickey M.J. Wright M.D. The many and varied roles of tetraspanins in immune cell recruitment and migration. Front. Immunol. 2018 9 1644 10.3389/fimmu.2018.01644 30072994
    [Google Scholar]
  20. Hadwen B. Stranges S. Barra L. Risk factors for hypertension in rheumatoid arthritis patients–A systematic review. Autoimmun. Rev. 2021 20 4 102786 10.1016/j.autrev.2021.102786 33609791
    [Google Scholar]
  21. Kitas G.D. Gabriel S.E. Cardiovascular disease in rheumatoid arthritis: State of the art and future perspectives. Ann. Rheum. Dis. 2011 70 1 8 14 10.1136/ard.2010.142133 21109513
    [Google Scholar]
  22. Stoll S. Wang C. Qiu H. DNA methylation and histone modification in hypertension. Int. J. Mol. Sci. 2018 19 4 1174 10.3390/ijms19041174 29649151
    [Google Scholar]
  23. Huang D. Shang W. Xu M. Genome-wide methylation analysis reveals a KCNK3 -Prominent causal cascade on hypertension. Circ. Res. 2024 135 3 e76 e93 10.1161/CIRCRESAHA.124.324455 38841840
    [Google Scholar]
  24. Holmes L. Lim A. Comeaux C.R. Dabney K.W. Okundaye O. DNA methylation of candidate genes (ACE II, IFN-γ, AGTR 1, CKG, ADD1, SCNN1B and TLR2) in essential hypertension: A systematic review and quantitative evidence synthesis. Int. J. Environ. Res. Public Health 2019 16 23 4829 10.3390/ijerph16234829 31805646
    [Google Scholar]
  25. Bai C. Su M. Zhang Y. Oviductal glycoprotein 1 promotes hypertension by inducing vascular remodeling through an interaction with MYH9. Circulation 2022 146 18 1367 1382 10.1161/CIRCULATIONAHA.121.057178 36172862
    [Google Scholar]
  26. Sun G. Chen J. Ding Y. A bioinformatics perspective on the links between tetraspanin-enriched microdomains and cardiovascular pathophysiology. Front. Cardiovasc. Med. 2021 8 630471 10.3389/fcvm.2021.630471 33860000
    [Google Scholar]
  27. Coskun Benlidayi I. Exercise therapy for improving cardiovascular health in rheumatoid arthritis. Rheumatol. Int. 2023 44 1 9 23 10.1007/s00296‑023‑05492‑2 37907642
    [Google Scholar]
  28. Yu K.H. Chen H.H. Cheng T.T. Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis. Medicine (Baltimore) 2022 101 1 e28501 10.1097/MD.0000000000028501 35029907
    [Google Scholar]
  29. Yu R. Liu X. Deng X. Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis. Front. Immunol. 2023 14 1211790 10.3389/fimmu.2023.1211790 37662936
    [Google Scholar]
  30. Raterman H.G. Bultink I.E. Lems W.F. Osteoporosis in patients with rheumatoid arthritis: An update in epidemiology, pathogenesis, and fracture prevention. Expert Opin. Pharmacother. 2020 21 14 1725 1737 10.1080/14656566.2020.1787381 32605401
    [Google Scholar]
  31. Qin Y. Wang Y. Meng F. Identification of biomarkers by machine learning classifiers to assist diagnose rheumatoid arthritis-associated interstitial lung disease. Arthritis Res. Ther. 2022 24 1 115 10.1186/s13075‑022‑02800‑2 35590341
    [Google Scholar]
  32. McInnes I.B. Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 2017 389 10086 2328 2337 10.1016/S0140‑6736(17)31472‑1 28612747
    [Google Scholar]
  33. Chen Sangerbox 2: Enhanced functionalities and update for a comprehensive clinical bioinformatics data analysis platform. iMeta 2024 3 e238 10.1002/imt2.238.
    [Google Scholar]
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CD82 Methylation Patterns in Inflammatory Arthritis and their Clinical Association with Hypertension in Rheumatoid Arthritis
Bentham Science Publishers ; https://doi.org/10.2174/0115665240371789250425113320
/content/journals/cmm/10.2174/0115665240371789250425113320
/content/journals/cmm/10.2174/0115665240371789250425113320
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  • Article Type:     Research Article
Keywords: hypertension ; cg22143324 ; Rheumatoid arthritis ; CD82 ; clinical association ; DNA methylation

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