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Vitamin D supplementation in systemic lupus erythematosus: relationship to disease activity, fatigue and the interferon signature gene expression.

Magro Rosalie, Saliba Christian, Camilleri Liberato, Scerri Christian, Borg Andrew A

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# Vitamin D Supplementation in Systemic Lupus Erythematosus

This prospective study investigated whether treating vitamin D deficiency and insufficiency improves outcomes in systemic lupus erythematosus (SLE) patients. Thirty-one SLE patients received vitamin D3 supplementation (8000 IU daily for 4–8 weeks followed by 2000 IU maintenance) and were assessed at baseline, 6 months, and 12 months for disease activity, fatigue, and interferon signature gene expression.

At 12 months, the study observed significant improvement in disease activity measured by SLEDAI-2K (p = 0.028) and a trend toward improved fatigue (p = 0.071). Anti-dsDNA antibody titers also decreased significantly (p = 0.045). While mean interferon signature gene expression scores declined from baseline to 6 months, this change did not reach statistical significance (p = 0.165).

The findings suggest that vitamin D supplementation may reduce disease activity and fatigue in vitamin D-deficient or insufficient SLE patients, potentially through suppression of interferon-mediated immune responses. The results support evaluation of vitamin D repletion as an adjunctive therapeutic strategy in SLE management.

Abstract

BACKGROUND: In addition to the well-known role of vitamin D in calcium homeostasis and bone metabolism, vitamin D is important in the modulation of the immune system and inflammatory processes. Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE), possibly as a result of sun avoidance. The aim of this prospective open-label study was to assess the effect of the treatment of vitamin D deficiency and insufficiency in SLE patients, particularly with regards to disease activity, fatigue and interferon signature gene expression. METHODS: 31 SLE patients, 13 with vitamin D deficiency and 18 with vitamin D insufficiency were treated with vitamin D3. They were supplemented with vitamin D3 8000 IU daily for 8 weeks if they were vitamin D deficient, or 8000 IU daily for 4 weeks if they were insufficient. This was followed by 2000 IU daily maintenance. They were assessed at baseline, after 6 and 12 months by means of an interview, filling in questionnaires and blood tests. The expression of 12 interferon signature genes in RNA extracted from whole blood was measured by using QuantiGene Plex technology. RESULTS: An improvement in disease activity measured by systemic lupus erythematosus disease activity index-2K (SLEDAI-2K; p = 0.028) and fatigue measured by fatigue severity scale (FSS; p = 0.071) at 12 months were noted. A significant decrease in anti-double stranded deoxyribonucleic acid (dsDNA) titre (p = 0.045) was also noted. The mean interferon signature gene expression score decreased from baseline to 6 months, however statistical significance was not achieved (p = 0.165). CONCLUSIONS: Improved disease activity and fatigue have been noted when Vitamin D has been supplemented in vitamin D deficient/insufficient SLE patients. One possible mechanism could be the suppression of the interferon signature gene expression. TRIAL REGISTRATION: The study was registered with the ISRCTN registry on 12/04/2021 (Trial ID: ISRCTN59058825).