Associations of site-specific CD4 + -T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus

• Published in: Lupus 2021-01, Vol.30 (1), p.45-51
• Main Authors: Vordenbäumen, Stefan, Rosenbaum, Anna, Gebhard, Claudia, Raithel, Johanna, Sokolowski, Alexander, Düsing, Christina, Chehab, Gamal, Richter, Jutta G, Brinks, Ralph, Rehli, Michael, Schneider, Matthias
• Format: Article
• Language: English
• Subjects: CD4 antigen; CD40 antigen; CD40L protein; CpG islands; Deoxyribonucleic acid; DNA; Ligands; Lupus; Lymphocytes T; Systemic lupus erythematosus
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203320965690

Objective To comprehensively assess associations of site-specific CD4+-T-cell hypomethylation of the CD40-Ligand gene (CD40L) with disease activity of women with systemic lupus erythematosus (SLE). Methods CpG-sites within the DNA of the promotor and two enhancer regions (n = 22) of CD40L were identified and numbered consecutively. The rate of methylated DNA in isolated CD4+-T-cells of women with SLE were quantified for each methylation site by MALDI-TOF. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Associations of site-specific methylation rates with the SLEDAI scores were assessed by linear regression modelling. P values were adjusted according to Bonferroni-Holm as indicated. Results 60 female SLE patients participated in the study (age 45.7 ± 11.1 years, disease duration 17.0 ± 8.3 years). Significant associations to the SLEDAI were noted for CpG22 hypomethylation of the promotor (β = −40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (β = −30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (β = 15.0, p = 0.046, adjusted p = 0.8). Conclusion Site-specific hypomethylation of the CD40L promotor in CD4+-T-cells show associations with disease activity in female SLE patients.