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

Vordenbaeumen, Stefan and Rosenbaum, Anna and Gebhard, Claudia and Raithel, Johanna and Sokolowski, Alexander and Duesing, Christina and Chehab, Gamal and Richter, Jutta G. and Brinks, Ralph and Rehli, Michael and Schneider, Matthias (2021) Associations of site-specific CD4(+)-T-cell hypomethylation within CD40-ligand promotor and enhancer regions with disease activity of women with systemic lupus erythematosus. LUPUS, 30 (1). pp. 45-51. ISSN 0961-2033, 1477-0962

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Abstract

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 (beta = -40.1, p = 0.017, adjusted p = 0.027), trends were noted for CpG17 hypomethylation of the promotor (beta = -30.5, p = 0.032, adjusted p = 0.6), and for CpG11 hypermethylation of the second enhancer (beta = 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.

Item Type: Article
Uncontrolled Keywords: ; Systemic lupus erythematosus; CD40-ligand; methylation; epigenetics; disease activity; T-cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Sep 2022 13:48
Last Modified: 07 Sep 2022 13:48
URI: https://pred.uni-regensburg.de/id/eprint/46833

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