Nervous system autoantibodies and vitamin D receptor gene polymorphisms in hemodialysis patients.
Nervous system autoantibodies and vitamin D receptor gene polymorphisms in hemodialysis patients.
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血液透析患者神经系统自身抗体和维生素D受体基因多态性。
DOI：
10.1111/j.1542-4758.2012.00727.x
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
El-Fawal,HassanAN
中科院分区：
文献类型：
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作者：
Mason,DariusL;Assimon,MagdaleneM;Bishop,JeffreyR;El-Fawal,HassanAN
认知缺陷在血液透析（HD）患者中普遍存在。维生素D缺乏和维生素D受体（VDR）基因单核苷酸多态性（SNP）分别与神经退行性（ND）和神经保护有关。髓鞘碱性蛋白（MBP）、胶质细胞酸性蛋白（GFAP）和神经丝（NF）三联体蛋白的自身抗体（Ab）继发于神经系统（NS）损伤，提供了评估神经损伤的方法。对HD患者NS损伤的Ab生物标志物、其与VDRSNPs和营养性维生素D（NVD）治疗的相关性进行了表征。对接受麦角钙化醇治疗的HD患者（n=40）和未使用麦角钙化醇治疗的HD患者（n=71）的VDR基因型、细胞因子和Ab标记蛋白进行比较。通过免疫测定法测定白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和免疫球蛋白G（IgG）对NF、GFAP和MBP的滴度，并对受试者进行VDRSNPs BsmI（rs 1544410）和FokI（rs 2228570）基因分型。BsmI C等位基因携带者受试者（年龄63.3 ± 16.1岁，66%为男性）的NF-68抗体滴度较高（p = 0.027）。麦角钙化醇使用者（n = 40）与非使用者（n = 71）相比，对NS蛋白的Ab滴度较低;然而，只有抗NF-160和抗MBP滴度显著较高（p < 0.05）。HD患者中抗NS蛋白的IgG提示神经元和神经胶质损伤以及与VDR等位基因的关系。NVD可能提供一定的神经保护作用，表现为抗NF-160和抗MBP，在麦角钙化醇患者中显著降低。这项初步研究表明，抗体检测可能是有用的监测ND和NVD的神经保护HD患者的潜力。
Cognitive deficits are prevalent in hemodialysis (HD) patients. Vitamin D deficiency and vitamin D receptor (VDR) gene single nucleotide polymorphism (SNPs) have been linked to both neurodegeneration (ND) and neuroprotection, respectively. Autoantibodies (Ab) to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) triplet proteins arise secondary to nervous system (NS) damage providing a means to assess neurological injury. Characterization of Ab biomarkers of NS damage in HD patients, their association withVDRSNPs, and nutritional vitamin D (NVD) therapy was performed. VDRgenotypes,cytokines,andAb biomarkerstoNS proteins in HD subjects receivingergocalciferol (n=40) were compared with nonusers (n=71). Interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and immunoglobulin G (IgG) titers against NFs, GFAP, and MBP were measured by immunoassay.Subjectswere genotyped forVDRSNPsBsmI(rs1544410) andFokI(rs2228570). Subjects (age 63.3 ± 16.1 years, 66% male) who were C allele carriers ofBsmIhad higher values of NF‐68 antibody titers (p = 0.027). Ergocalciferol users (n = 40) compared with nonusers (n = 71) had lower Ab titers to NS proteins; however, only anti–NF‐160 and anti‐MBP titers were significantly (p < 0.05) higher. IgG against NS proteins in HD patients suggests neuronal and glial insult and a relationship withVDRalleles. NVD may provide some neuroprotection, indicated by anti–NF‐160 and anti‐MBP, which was markedly lowered in ergocalciferol patients. This preliminary study suggests that Ab detection may be useful in monitoring ND and the potential of NVD for neuroprotection in HD patients.