Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study. (October 2021)

• Record Type: Journal Article
• Authors: Vordenbäumen, Stefan; Sokolowski, Alexander; Rosenbaum, Anna; Gebhard, Claudia; Raithel, Johanna; Düsing, Christina; Chehab, Gamal; Richter, Jutta G; Brinks, Ralph; Rehli, Michael; Schneider, Matthias
• Is Part Of: Lupus. Volume 30:Number 11(2021)
• Page Start: 1773
• Page End: 1780
• Publication Date: 2021-10
• Subjects: Systemic lupus erythematosus -- nutrition -- methylation -- CD40-ligand -- T-cells -- disease activity; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1177/09612033211034559
• Languages: English
• ISSNs: 0961-2033

Abstract

Objective: Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE. Methods: Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg. Results: Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L . Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes. Conclusions: Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.