Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner
{"title":"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","authors":"Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner","doi":"10.1111/jns.12571","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and Aims</h3>\n \n <p>Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent <i>Campylobacter jejuni</i> 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 (p22<sup>phox</sup>) on acute severity, axonal damage, and recovery in adult GBS patients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within <i>CYBA</i> 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>CYBA</i> genotypes linked to reduced formation of ROS, i.e. rs1049254/<b>G</b> and rs4673/<b>A</b>, 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 <i>CYBA</i> alleles associated with high formation of ROS.</p>\n </section>\n \n <section>\n \n <h3> Interpretation</h3>\n \n <p>These findings implicate NOX-derived ROS in GBS pathophysiology and <i>CYBA</i> alleles as biomarkers of severity.</p>\n </section>\n </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12571","citationCount":"0","resultStr":"{\"title\":\"CYBA allelic variants are associated with severity and recovery in Guillain–Barré syndrome\",\"authors\":\"Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner\",\"doi\":\"10.1111/jns.12571\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and Aims</h3>\\n \\n <p>Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent <i>Campylobacter jejuni</i> 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 (p22<sup>phox</sup>) on acute severity, axonal damage, and recovery in adult GBS patients.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within <i>CYBA</i> 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p><i>CYBA</i> genotypes linked to reduced formation of ROS, i.e. rs1049254/<b>G</b> and rs4673/<b>A</b>, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. 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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.
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.