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探讨维生素 D 补充对复发缓解型多发性硬化症患者抗 EBV 抗体应答的影响。

Exploring the effect of vitamin D supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

机构信息

School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands/Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The Netherlands/Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands.

School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands/Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The Netherlands.

出版信息

Mult Scler. 2018 Sep;24(10):1280-1287. doi: 10.1177/1352458517722646. Epub 2017 Jul 21.

Abstract

BACKGROUND

Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS).

OBJECTIVES

To investigate the effect of high-dose vitamin D supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels.

METHODS

This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored.

RESULTS

The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures.

CONCLUSION

High-dose vitamin D supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.

摘要

背景

EB 病毒(EBV)感染和维生素 D 不足是多发性硬化症(MS)的潜在相互作用的危险因素。

目的

研究大剂量维生素 D 补充剂对复发性缓解型多发性硬化症(RRMS)患者针对 EBV 核抗原-1(EBNA-1)的抗体水平的影响,并探讨影响抗 EBNA-1 抗体水平的潜在机制。

方法

本研究利用 RRMS 患者的随机对照试验中的血液样本,这些患者在 48 周内接受维生素 D(14,000 IU/天;n = 30)或安慰剂(n = 23)治疗。测量循环 25-羟维生素 D 水平以及抗 EBNA-1、抗 EBV 衣壳抗原(VCA)和抗巨细胞病毒(CMV)抗体的水平。还探索了白细胞中的 EBV 载量、EBV 特异性细胞毒性 T 细胞反应以及体外抗 EBNA-1 抗体的产生。

结果

与安慰剂组(432(351-1280)至 429(297-1290)U/mL)相比,维生素 D 组的 EBNA-1 抗体水平(526(368-1683)至 455(380-1148)U/mL)中位数明显降低(p = 0.023),但 VCA 和 CMV 抗体水平没有明显降低。EBV 载量和细胞毒性 T 细胞反应不受影响。B 细胞培养中抗 EBNA-1 抗体水平仍低于检测限。

结论

大剂量维生素 D 补充剂选择性降低 RRMS 患者的抗 EBNA-1 抗体水平。我们的探索性研究并不暗示针对 EBV 的免疫反应增强是潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3689/6108041/b52775bcd8e9/10.1177_1352458517722646-fig1.jpg

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