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

Objective: To comprehensively assess associations of site-specific CD4-T-cell hypomethylation of the CD40-Ligand gene () 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 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 promotor in CD4-T-cells show associations with disease activity in female SLE patients.