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抗N-甲基-D-天冬氨酸受...炎脑脊液生物标志物研究进展_丁晓.pdf
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甲基 天冬氨酸 脑脊液 生物 标志 研究进展 丁晓
lymphoproliferative disorder with risk to develop a systemic lymphoma J.Blood,2013,122(18):3101-3110.18 COHEN J I,MANOLI I,DOWDELL K,et al.Hydroa vacciniforme-like lymphoproliferative disorder:an EBV disease with a low risk of systemic illness in whites J.Blood,2019,133(26):2753-2764.19 PLAZA J A,SANGUEZA M.Hydroa vacciniforme-like lymphoma with primarily periorbital swelling:7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma J.Am J Dermatopathol,2015,37(1):20-25.20 MAGAA M,MASSONE C,MAGAA P,et al.Clinicopathologic features of hydroa vacciniforme-like lymphoma:a series of 9 patients J.Am J Dermatopathol,2016,38(1):20-25.21 REN F,ZHU J,PERRY D M,et al.Hydroa vacciniforme-like lymphoproliferative disorder:a retrospective cohort study of seven pediatric cases J.Int J Dermatol,2020,59(8):e290-e292.22 RUAN Y P,SHEN X Y,SHI R F,et al.Hydroa vacciniforme-like lymphoproliferative disorder treated with intravenous immunoglobulin:long-term remission without haematopoietic stem cell transplantation or chemotherapy J.Advances in dermatology and venereology,2020,100(13):adv00192.23 SAID J,SMART C.Severe mosquito bite allergy:an unusual EBV+NK cell lymphoproliferative disorder J.Blood,2019,133(9):999.24 LEE S,PARK C J,CHO Y U,et al.The first Korean case of Epstein-Barr virus-positive natural killer/T-cell lymphoma that progressed from severe mosquito bite allergy,with coexistence of hemophagocytic lymphohistiocytosis J.Ann Lab Med,2020,40(1):80-83.25 LEE W I,LIN J J,HSIEH M Y,et al.Immunologic difference between hypersensitivity to mosquito bite and hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection J.PLoS One,2013,8(10):1-9.26 CHEN Z H,WANG M,GUAN P J,et al.Comparison of systemic EBV-positive T-Cell and NK-cell lymphoproliferative diseases of childhood based on classification evolution:new classification,old problems J.Am J Surg Pathol,2020,44(8):1061-1072.27 MONTES-MOJARRO I A,KIM W Y,FEND F,et al.Epstein-Barr virus positive T and NK-cell lymphoproliferations:morphological features and differential diagnosis J.Semin Diagn Pathol,2020,37(1):32-46.28 COHEN J I,IWATSUKI K,KO Y H,et al.Epstein-Barr virus NK and T cell lymphoproliferative disease:report of a 2018 international meeting J.Leuk Lymphoma,2020,61(4):808-819.29 COFFEY A M,LEWIS A,MARCOGLIESE A N,et al.A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood:a single tertiary care pediatric institution experience in North America J.Pediatr Blood Cancer,2019,66(8):1-12.30 QUINTANILLA-MARTINEZ L,KUMAR S,FEND F,et al.Fulminant EBV(+)T-cell lymphoproliferative disorder following acute/chronic EBV infection:a distinct clinicopathologic syndrome J.Blood,2000,96(2):443-451.31 PARK S,KO Y H.Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders J.J Dermatol,2014,41(1):29-39.32 OHSHIMA K,KIMURA H,YOSHINO T,et al.Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder(LPD)in children and young adults:overlap with chronic active EBV infection and infantile fulminant EBV T-LPD J.Pathol Int,2008,58(4):209-217.33 KIMURA H,ITO Y,KAWABE S,et al.EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts:prospective analysis of 108 cases J.Blood,2012,119(3):673-686.(编辑:刘雄志)(收稿日期:2021-01-07 修回日期:2021-02-16)doi:10.13407/ki.jpp.1672-108X.2023.07.015综述抗抗 N N-甲甲基基-D D-天天冬冬氨氨酸酸受受体体脑脑炎炎脑脑脊脊液液生生物物标标志志物物研研究究进进展展丁晓 综述,蒋莉 审校(重庆医科大学附属儿童医院,儿童发育疾病研究教育部重点实验室,儿童发育重大疾病国家国际科技合作基地,儿科学重庆市重点实验室,重庆 400014)作者简介:丁晓(1994.12-),女,硕士,主要从事儿童神经系统疾病研究,E-mail:2273611839 。中图分类号R748 文献标识码A 文章编号1672-108X(2023)07-0054-05Progress of Cerebrospinal Fluid Biochemical Markers of Anti-N-Methyl-D-Aspartate Receptor EncephalitisDing Xiao,Jiang Li(Children s Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)45儿科药学杂志 2023 年第 29 卷第 7 期 Journal of Pediatric Pharmacy 2023,Vol.29,No.7 抗 N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎是由靶向 NMDAR GluN1 亚基的 IgG 抗体所介导的自身免疫性脑炎,约占自身免疫性脑炎的 80%,多见于青少年和年轻女性。患者通常会出现精神行为异常、语言障碍、癫痫发作、运动障碍、意识水平下降、自主神经功能障碍或中枢性通气不足等六大临床表现。虽然 80%以上患者远期预后良好,但是该病康复过程漫长且多变,病死率为 5%7%1-3。此外,通气不足及血压不稳定等自主神经功能紊乱可能在病程后期出现,并有造成长期及严重后遗症的风险。目前该病的治疗方案尚无统一标准,临床医师通常通过个人经验来判断是等待一线免疫治疗的反应还是立即转向更积极地免疫治疗。有研究1-2表明,越早启动二线治疗,预后越好,但由于二线免疫治疗费用较高且感染机会较大,因此决定启动下一步治疗方案的时机必须及时且适当。早期可获得的检查如脑电图、头颅核磁共振(MRI)、脑脊液常规检查对该病的特异性不高,抗 NMDAR 抗体作为该病的致病抗体,通过与广泛分布于中枢神经系统,尤其是海马和大脑皮层的 NMDAR 相结合,引起 NMDAR 的选择性交联和内化,导致 NMDAR 介导的突触电流的减少,进而引起该受体所调控的行为、认知、记忆、学习等功能障碍4,并且这些效应与抗体滴度相关5,脑脊液抗体滴度可能反映疾病的严重程度及预后6。但抗体滴度变化较慢且有患者完全康复后长达 15年仍可在脑脊液中检测到抗体7,表明抗体滴度与病程严重程度及疾病活动度并不完全相关,在判断预后和选择治疗方案方面需要其他生物标志物来帮助。近年来研究发现,脑脊液中多种生物标志物在抗 NMDAR 脑炎的治疗效果评估、活动性监测、预后评估等方面可能有一定的作用。本文将对其研究现状进行综述。1 脑脊液标志物1.1 CXCL13CXCL13 是一

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