Characterisation of the relationship between fatigue, Vitamin D level, disease activity and interferon signature gene expression in systemic lupus erythematosus : a population based study

Ph.D.(Melit.) ; Vitamin D deficiency and fatigue are highly prevalent in Systemic Lupus Erythematosus (SLE). The main aim of this research was to analyse the relationship between vitamin D, fatigue, disease activity and interferon (IFN) signature gene expression in SLE. 92 patients with SLE were interviewed, had blood and urine tests, and filled questionnaires. Subsequently, 13 patients with vitamin D deficiency and 20 with vitamin D insufficiency were supplemented with vitamin D3. They were re-evaluated after 6 and 12 months. The expression of 12 IFN signature genes in blood at baseline and at 6 months was measured. In the final part of the research, the in vitro effect of calcitriol on the IFN signature gene expression in macrophages and dendritic cells was analysed. 56.5% of participants in the cross-sectional cohort had a high degree of fatigue (fatigue severity scale (FSS) >3.7). The strongest predictors of fatigue were depression (p<0.001) and pain (p<0.001) and no correlation with serum 25-hydroxyvitamin D and IFN signature gene expression was found. Higher disease activity measured by SLE disease activity index-2K (SLEDAI-2K) was noted in patients who were homozygous for the minor allele for the vitamin D receptor (VDR) polymorphism BsmI (p=0.046). In the prospective study, an improvement in SLEDAI-2K (p=0.028) and FSS (p=0.011) at 12 months were noted. The mean IFN signature gene expression score decreased from baseline to 6 months (from 2.69 to 2.10, p=0.083), and the IFN signature gene expression decreased for all 12 genes especially OAS1 (p=0.032) and SOCS1 (p=0.005). In the in vitro experiment, a significant reduction in IFN score was noted in dendritic cell and macrophage samples with calcitriol (p=0.014, p=0.012). This was also the case for Interferon Regulatory Factor (IRF) 8 expression in the macrophage culture (p<0.001). Vitamin D supplementation in SLE resulted in improved disease activity and fatigue. This could be explained by the suppression of the IFN signature gene expression, ...