الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 9 |  |  |
| | | from | 9 | | |
Abstract
SLE is a systemic autoimmune disease. It can cause chronic inflammation & damage in several tissues and organs. Genetic susceptibility and environmental factors are both responsible for the pathogenesis of SLE. Vitamin D deficiency is one of such factors.
Vitamin D, as a steroid hormone, exhibits regulatory effects on growth, proliferation, apoptosis and function of the immune system cells. Vitamin D is associated with pathophysiology of SLE. The discovery of vitamin D receptor expression by cells of the immune system has spurred more research on the immunomodulatory properties of vitamin D over the past decade.
Vitamin D levels were correlated with different health conditions, including SLE in children. Vitamin D action is mediated through VDR, which acts as a transcription factor. The human VDR gene is located in chromosome 12 and contains 14 exons and spans approximately 75kb. VDR gene promoter is embedded in a GC-rich island.
The transcriptional activity of VDR could be affected by epigenetic mechanisms such as DNA methylation which regulate gene expression and chromatin structure. Methylation of CpG islands located at gene promoters typically inhibits gene expression of active transcribed genes of VDR.
The aim of the present work was to study the methylation status of VDR gene promoter and serum levels of 25-hydroxyvitamin D (25(OH) D) and their clinical significance in patients with SLE. The Study was conducted on 2 groups; 40 patients of children with SLE and 40 age and sex matched children.
The study was conducted on pediatrics presented to Alexandria University Children Hospital.
All the patients included in the study were subjected to the following:
• Full history taking.
• Complete Physical examination.
• Laboratory investigations:
• Complete Blood Count.
• Serum Urea, Creatinine.
• Serum Calcium and phosphorus.
• Alkaline phosphatase.
• C-reactive protein.
• Serum albumin.
• Liver enzymes (ALT, AST).
• Urine protein creatinine ratio.
• Anti-nuclear antibody (ANA) titre and pattern using immunofluorescence technique.
• Anti-double strand DNA(Anti dsDNA) by ELISA.
• Complement (C3, C4) by nephelometry.
• Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) will be recorded.
• Measurement of vitamin D (25(OH) D) by Enzyme Linked Fluorescent Assay (ELFA) technique.
• Vitamin D Receptor Methylation Assay by Quantitative Methylation specific PCR (qMS-PCR).
The patient group included 6 males (15%) and 34 females (85%), while the control group included 13 males (32.5%) and 27 females (67.5%). The age of the patient group ranged between 8.0 – 18.0 years with a mean ± SD of 14.10 ± 3.02 years. While the age of the control group ranged between 9.0 – 18.0 years with a mean ± SD of 13.43 ± 2.84 years.
The height was significantly lower in the patient group than the control group. The weight was significantly lower in the patient group than the control group. The BMI was significantly lower in the patient group than the control group.
No significant difference was detected between patient group with SLE and control group regarding CBC parameters.
BUN was significantly higher in the patient group than the control group. The serum creatinine was significantly higher in the patient group than the control group.
Calcium level was significantly lower in the SLE patient group than the control group. The serum phosphorus was significantly lower in the SLE patient group than the control group.
The serum albumin was significantly higher in the control group than the SLE patient group. ALT was significantly higher in the SLE patient than the control group. AST was significantly higher in the control group than the patient group. ALP was significantly higher in the SLE patient group than the control group.
CRP was significantly higher in the patient group than the control group. The vitamin D level was significantly lower in the SLE patient group than the control group. Among the patient group, 24 patients (60%) showed flare according to SLEDAI. SLEDAI score ranged between 0– 26.0.
The methylation level was significantly higher in the SLE patient group than the control group. There was a significant negative correlation between methylation level and vitamin D level. Also there was a significant negative correlation between methylation level and serum Ca level. There was a significant positive correlation between methylation level and SLEDAI score.
There was a significant positive correlation between vitamin D level and serum Ca level. On the other hand, there was a significant negative correlation between vitamin D level and SLEDAI score.