CYBA等位基因变异与格林-巴-巴综合征的严重程度和恢复有关

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Journal of the Peripheral Nervous System Pub Date : 2023-06-08 DOI:10.1111/jns.12571
Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner
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引用次数: 0

摘要

背景和目的吉兰-巴勒综合征(GBS)是一种罕见的急性神经病变,以上升肌无力为特征。年龄、轴突GBS变异和先前的空肠弯曲杆菌感染与严重的GBS有关,但神经损伤的详细机制仅被部分探索。促炎髓细胞表达NADPH氧化酶(NOX),产生与神经退行性疾病有关的组织毒性活性氧(ROS)。本研究分析了编码功能性NOX亚基CYBA (p22phox)的基因变异对成人GBS患者急性严重程度、轴突损伤和康复的影响。方法提取121例患者的DNA,采用实时定量聚合酶链反应对CYBA中rs1049254和rs4673等位基因变异进行基因分型。采用单分子阵列法定量血清神经丝轻链。随访患者的严重程度和运动功能恢复长达13年。结果与ROS形成减少相关的CYBA基因型rs1049254/G和rs4673/A与无辅助通气、较短的血清神经丝轻链正常化时间和较短的运动功能恢复时间显著相关。随访时的残障局限于携带与ROS高形成相关的CYBA等位基因的患者。这些发现暗示GBS病理生理和CYBA等位基因中nox衍生的ROS是严重程度的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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CYBA allelic variants are associated with severity and recovery in Guillain–Barré syndrome

Background and Aims

Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22phox) on acute severity, axonal damage, and recovery in adult GBS patients.

Methods

Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years.

Results

CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/G and rs4673/A, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS.

Interpretation

These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.

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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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