Department of Rheumatology, Rheinisches Rheuma-Zentrum St. Elisabeth-Hospital, Meerbusch-Lank, Germany.
Medical Faculty, Dept. & Hiller Research Unit for Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany.
Lupus. 2021 Oct;30(11):1773-1780. doi: 10.1177/09612033211034559. Epub 2021 Jul 20.
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.
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.
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 (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 . Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes.
Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.
CD40 配体（CD40L）在 T 细胞中的低甲基化与系统性红斑狼疮（SLE）的疾病活动度增加有关。因此，我们研究了饮食甲基供体和产物与 SLE 中 CD40L 甲基化状态的可能关联。
采用食物频率问卷计算 61 名女性 SLE 患者（年龄 45.7±12.0 岁，病程 16.2±8.4 年）的甲基供体微量营养素，并与 T 细胞 CD40L 启动子中先前鉴定的关键 DNA 甲基化位点（CpG17 和 CpG22）的甲基化水平进行比较，采用 EpiTYPER 质谱分析平台进行定量 DNA 甲基化分析。采用 SLE 疾病活动指数（SLEDAI）评估疾病活动度。采用线性回归模型。根据 Benjamini 和 Hochberg 进行 P 值调整。
在所评估的微量营养素（每天 g）中，蛋氨酸和半胱氨酸与 CpG17 的甲基化相关（β=5.0（95%CI：0.6-9.4），p=0.04；β=2.4（0.6-4.1），p=0.02）。蛋氨酸、胆碱和半胱氨酸与整个的平均甲基化也相关（β=9.5（1.0-18.0），p=0.04；β=1.6（0.4-3.0），p=0.04；β=4.3（0.9-7.7），p=0.02）。SLEDAI 与 CpG17（β=-32.6（-60.6 至-4.6），p=0.04）和 CpG22（β=-38.3（-61.2 至-15.4），p=0.004）的低甲基化均有确认的关联，但与的平均甲基化没有关联。对甲基化影响最大的饮食产物包括肉类、冰淇淋、白面包和煮土豆。
饮食甲基供体可能影响 SLE 中 DNA 甲基化水平和疾病活动度。
