scholarly journals THU0235 VITAMIN D AND INTERFERON SIGNATURE GENE EXPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 344.3-345
Author(s):  
R. Magro ◽  
C. Saliba ◽  
L. Camilleri ◽  
C. Scerri ◽  
A. Borg

Background:Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance.1The potential negative impact of vitamin D deficiency on SLE disease activity has been shown in a number of studies.2The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease.3Objectives:The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients.Methods:Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood samples were taken. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee.Results:92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D <20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p=0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K.Conclusion:This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth.References:[1]Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006; 5: 114-7.[2]Sahebari M, Nabavi N, Salehi M. Correlation between serum 25(OH)D values and lupus disease activity: an original article and a systematic review with meta-analysis focusing on serum VitD confounders.Lupus2014; 23: 1164-77.[3]Arasappan D, Tong W, Mummaneni P, Fang H, Amur S. Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells. BMC Med. 2011; 9: 65.Disclosure of Interests: :None declared

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Rosalie Magro ◽  
Christian Saliba ◽  
Liberato Camilleri ◽  
Christian Scerri ◽  
Andrew A Borg

Abstract Background Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance. The potential negative impact of vitamin D deficiency on the disease activity of SLE has been shown in a number of studies. The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease. The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients. Methods Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood tests including full blood count, renal profile, calcium, 25-hydroxyvitamin D, complement 3 (C3), complement 4 (C4) and anti-double standed DNA (anti-dsDNA) titre were carried out. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee. Results 92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D &lt; 20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p = 0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K. Conclusion This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth. Disclosures R. Magro None. C. Saliba None. L. Camilleri None. C. Scerri None. A.A. Borg None.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Rosalie Magro ◽  
Christian Saliba ◽  
Liberato Camilleri ◽  
Christian Scerri ◽  
Andrew A. Borg

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).


2011 ◽  
Vol 70 (4) ◽  
pp. 399-407 ◽  
Author(s):  
Leanne C. Breslin ◽  
Pamela J. Magee ◽  
Julie M. W. Wallace ◽  
Emeir M. McSorley

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease where genetic susceptibility coupled with largely undefined environmental factors is reported to underlie the aetiology of the disease. One such factor is low vitamin D status. The primary source of vitamin D is endogenous synthesis following exposure of the skin to UVB light. Photosensitivity, sunlight avoidance and the use of sun protection factor in combination with medications prescribed to treat the symptoms of the disease, puts SLE patients at increased risk of vitamin D deficiency. Decreased conversion of 25-hydroxyvitamin D to the metabolically active form, 1,25-dihydroxyvitamin D3, is possible, due to renal impairment common in SLE putting additional stress on vitamin D metabolism. The majority of studies have identified low 25-hydroxyvitamin D in SLE patients, albeit using varying cut-offs (<25 to <80 nmol/l). Of these studies, fifteen have investigated a link between status and disease activity with conflicting results. Variation with disease activity index measures used alongside methodological limitations within the study design may partially explain these findings. This review discusses the importance of optimal vitamin D status in SLE, critically evaluates research carried out to date that has investigated vitamin D in SLE, and highlights the need for a well-designed observational study that controls for diet, medication use, dietary supplements, UV exposure and seasonality, that uses sensitive methods for measuring vitamin D status and disease activity in SLE to conclusively establish the role of vitamin D in SLE.


2012 ◽  
Vol 33 (6) ◽  
pp. 1461-1467 ◽  
Author(s):  
Kittiwan Sumethkul ◽  
Smonporn Boonyaratavej ◽  
Tasanee Kitumnuaypong ◽  
Sungchai Angthararuk ◽  
Patcharin Cheewasat ◽  
...  

Author(s):  
Iu.V. Davydova ◽  
◽  
A.Y. Lymanskaya ◽  
O.M. Kravets ◽  
◽  
...  

The aim is to analyze the effectiveness of correction vitamin D deficiency in the treatment of anemia in women with systemic lupus erythematosus (SLE). Materials and methods. Concomitant documented levels of 25-hydroxyvitamin D, hemoglobin, ferritin, and serum iron in a group of women with SLE who applied for preconception counseling were analyzed. All women were in remission for SLE activity within 5 to 6 months. A total of 54 women were involved in iron metabolism disorders (decreased ferritin, hemoglobin, serum iron). Vitamin D deficiency was detected at <30 ng/ml, and anemia at hemoglobin <120 g/l. Group 1 consisted of 32 women with vitamin D levels <30 ng/ml who received antianemic therapy with ferrous sulfate with ascorbic acid, correction of vitamin D deficiency with Olidetrim 2000 U (Polpharma), and group 2 — women with vitamin D levels <30 ng/ml (n=22) who received antianemic therapy with ferrous sulfate with ascorbic acid and a vitamin complex containing vitamin D 400 U. The groups were comparable by the main demographic indicators (age, education, socio-economic level). In both groups, iron metabolism and 25-hydroxyvitamin D levels were monitored in 4 weeks after treatment. Results and conclusions. Women with SLE have a high risk of chronic inflammatory anemia development, which can be combined with iron deficiency anemia. To improve the results of treatment, it is proposed to introduce supplementation with a high dose of vitamin D (Olidetrim 2000 U), into complex therapy which contributes to the effectiveness of correction of deficiency of this vitamin, as well as the onset of long-term recovery of iron store, hemoglobin concentration. The study was conducted in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of women was obtained for the research. The authors declare no conflict of interest. Key words: vitamin D deficiency, pregnant women, systemic lupus erythematosus, supplementation.


2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1699.1-1700
Author(s):  
F. Masini ◽  
K. Gjeloshi ◽  
E. Pinotti ◽  
F. Danzo ◽  
F. Guarino ◽  
...  

Background:The association between hyperuricemia and psoriatic arthritis (PsA) is actually generally accepted. Previous studies have demonstrated that uric acid suppress 25(OH)D metabolism [1]. More evidence is required to demonstrate the immune modulatory effects in psoriasis, psoriatic arthritis and other autoimmune diseases. In particular, the potential association between 25-hydroxyvitamin D serum levels and PsA still remains unknown.Objectives:To assess a clinical association between uric acid/25(OH)D serum levels ratio related to PASI, BASDAI and DAPSA, if any, in patients with psoriatic arthritis.Methods:We retrospectively observed 61 patients with psoriatic arthritis referred to our outpatients clinic, independently from already being on therapy or naïve. All selected patients underwent only conventional non-biological therapy at baseline and none received vitamin D supplementation and either allopurinol or febuxostat previously. Blood samples were drawn from all participants for assessment of 25-hydroxyvitamin D and uric acid serum levels. Disease activity of psoriasis and psoriatic arthritis were assessed by the Psoriasis Area and Severity Index (PASI), the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). We assessed the covariates of interest by the Wilcoxon non parametric test, through the SPSS 24 Software.Results:We observed 61 patients, mainly females (83.6%). At the univariate analysis, the uric acid/25(OH)D serum levels ratio revealed significantly associated with DAPSA and BASDAI indexes (p<0.001 and p<0.001, respectively), whilst no significant association emerged with the PASI index (p=0.462).Conclusion:Data in the literature about these associations in the context of psoriatic arthritis are really poor. As a consequence, our findings, though preliminary, suggest us to hypothesize a potential role of uric acid/25(OH)D serum levels ratio as potential inflammation marker in order to better assess the disease activity. However, future larger studies are needed to investigate more in depth this association.[1]Charoenngam N, Ponvilawan B, Ungprasert P. Vitamin D insufficiency and deficiency are associated with a higher level of serum uric acid: A systematic review and meta-analysis. Mod Rheumatol. 2019 Mar 4:1-6.Disclosure of Interests:None declared


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