High-mobility group box 1 as a predictive biomarker for drug-resistant epilepsy: A proof-of-concept study

被引:29
作者
Walker, Lauren Elizabeth [1 ]
Sills, Graeme John [1 ]
Jorgensen, Andrea [1 ]
Alapirtti, Tiina [2 ]
Peltola, Jukka [2 ]
Brodie, Martin J. [3 ]
Marson, Anthony Guy [1 ]
Vezzani, Annamaria [4 ]
Pirmohamed, Munir [1 ]
机构
[1] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England
[2] Tampere Univ Hosp, Dept Neurol & Rehabil, Tampere, Finland
[3] Western Infirm & Associated Hosp, Epilepsy Unit, Glasgow, Lanark, Scotland
[4] Mario Negri Inst Pharmacol Res, Sci Inst Res & Hlth Care, Dept Neurosci, Milan, Italy
基金
英国医学研究理事会;
关键词
biomarker; drug-resistant; epilepsy; HMGB1; neuroinflammation; TOLL-LIKE RECEPTOR;
D O I
10.1111/epi.17116
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Currently no sensitive and specific biomarkers exist to predict drug-resistant epilepsy. We determined whether blood levels of high-mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug-resistant epilepsies, identifies patients with drug-resistant seizures. Patients with drug-resistant epilepsy express significantly higher levels of blood HMGB1 than those with drug-responsive, well-controlled seizures and healthy controls. No correlation existed between blood HMGB1 levels and total pretreatment seizure count or days since last seizure at new epilepsy diagnosis, indicating that blood HMGB1 does not solely reflect ongoing seizures. HMGB1 distinguishes with high specificity and selectivity drug-resistant versus drug-responsive patients. This protein therefore has potential clinical utility to act as a biomarker for predicting response to therapy, which should be addressed in prospective clinical studies.
引用
收藏
页码:E1 / E6
页数:6
相关论文
共 16 条
[1]   HMGB1 Contributes to the Expression of P-Glycoprotein in Mouse Epileptic Brain through Toll-Like Receptor 4 and Receptor for Advanced Glycation End Products [J].
Chen, Yan ;
Huang, Xian-Jing ;
Yu, Nian ;
Xie, Yuan ;
Zhang, Kang ;
Wen, Fang ;
Liu, Hao ;
Di, Qing .
PLOS ONE, 2015, 10 (10)
[2]  
Kan MC, 2019, BRAZ J MED BIOL RES, V52, DOI [10.1590/1414-431X20197374, 10.1590/1414-431x20197374]
[3]   Evaluation of serum high-mobility group box 1 concentration in dogs with epilepsy: A case-control study [J].
Koo, Yoonhoi ;
Kim, Hakhyun ;
Yun, Taesik ;
Jung, Dong-In ;
Kang, Ji-Houn ;
Chang, Dongwoo ;
Na, Ki-Jeong ;
Yang, Mhan-Pyo ;
Kang, Byeong-Teck .
JOURNAL OF VETERINARY INTERNAL MEDICINE, 2020, 34 (06) :2545-2554
[4]   Anakinra usage in febrile infection related epilepsy syndrome: an international cohort [J].
Lai, Yi-Chen ;
Muscal, Eyal ;
Wells, Elizabeth ;
Shukla, Nikita ;
Eschbach, Krista ;
Hyeong Lee, Ki ;
Kaliakatsos, Marios ;
Desai, Nevedita ;
Wickstrom, Ronny ;
Viri, Maurizio ;
Freri, Elena ;
Granata, Tiziana ;
Nangia, Srishti ;
Dilena, Robertino ;
Brunklaus, Andreas ;
Wainwright, Mark S. ;
Gorman, Mark P. ;
Stredny, Coral M. ;
Asiri, Abdurhman ;
Hundallah, Khalid ;
Doja, Asif ;
Payne, Eric ;
Wirrell, Elaine ;
Koh, Sookyong ;
Carpenter, Jessica L. ;
Riviello, James .
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2020, 7 (12) :2467-2474
[5]   Drug resistance in brain diseases and the role of drug efflux transporters [J].
Löscher, W ;
Potschka, H .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (08) :591-602
[6]   Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures [J].
Maroso, Mattia ;
Balosso, Silvia ;
Ravizza, Teresa ;
Liu, Jaron ;
Aronica, Eleonora ;
Iyer, Anand M. ;
Rossetti, Carlo ;
Molteni, Monica ;
Casalgrandi, Maura ;
Manfredi, Angelo A. ;
Bianchi, Marco E. ;
Vezzani, Annamaria .
NATURE MEDICINE, 2010, 16 (04) :413-U91
[7]  
Pauletti A., 2019, Brain, V142, P39, DOI 10.1093/brain/awz130
[8]   High Mobility Group Box 1 is a novel pathogenic factor and a mechanistic biomarker for epilepsy [J].
Ravizza, Teresa ;
Terrone, Gaetano ;
Salamone, Alessia ;
Frigerio, Federica ;
Balosso, Silvia ;
Antoine, Daniel J. ;
Vezzani, Annamaria .
BRAIN BEHAVIOR AND IMMUNITY, 2018, 72 :14-21
[9]   Is the underlying cause of epilepsy a major prognostic factor for recurrence? [J].
Semah, F ;
Picot, MC ;
Adam, C ;
Broglin, D ;
Arzimanoglou, A ;
Bazin, B ;
Cavalcanti, D ;
Baulac, M .
NEUROLOGY, 1998, 51 (05) :1256-1262
[10]   Drug-Resistant epilepsy: Multiple Hypotheses, Few Answers [J].
Tang, Fei ;
Hartz, Anika M. S. ;
Bauer, Bjorn .
FRONTIERS IN NEUROLOGY, 2017, 8