抗N-甲基-D-天冬氨酸受体脑炎相关细胞因子的研究进展

郑雅心; 蒋莉

doi:10.7499/j.issn.1008-8830.2211125

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中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (3) : 321-327. DOI: 10.7499/j.issn.1008-8830.2211125

综述

抗N-甲基-D-天冬氨酸受体脑炎相关细胞因子的研究进展

郑雅心, 蒋莉

作者信息 +

Recent research on cytokines associated with anti-N-methyl-D-aspartate receptor encephalitis

ZHENG Ya-Xin, JIANG Li

Author information +

文章历史 +

摘要

抗N-甲基-D-天冬氨酸受体（N-methyl-D-aspartate receptor，NMDAR）脑炎为一类中枢神经系统自身免疫炎症性疾病，目前对其免疫机制知之甚少。脑脊液中除抗NMDAR抗体检测外，缺乏与疾病相关标志物，导致部分患者延误诊治。为此，近年针对细胞因子的研究不断增加，旨在评价其是否可作为新型生物标志物对疾病进行评估并协助诊治。现有研究表明部分细胞因子与抗NMDAR脑炎疾病进程可能相关，故该文就抗NMDAR脑炎相关细胞因子研究进展进行综述。

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory disease of the central nervous system, and little is known about its immune mechanism at present. There is a lack of disease-related biomarkers in cerebrospinal fluid except anti-NMDAR antibody, which leads to delayed diagnosis and treatment in some patients. Therefore, there has been an increasing number of studies on related cytokines in recent years to assess whether they can be used as new biomarkers for evaluating disease conditions and assisting diagnosis and treatment. Current studies have shown that some cytokines may be associated with the progression of anti-NMDAR encephalitis, and this article reviews the research advances in such cytokines associated with anti-NMDAR encephalitis.

导出引用

郑雅心, 蒋莉. 抗N-甲基-D-天冬氨酸受体脑炎相关细胞因子的研究进展[J]. 中国当代儿科杂志. 2023, 25(3): 321-327 https://doi.org/10.7499/j.issn.1008-8830.2211125

ZHENG Ya-Xin, JIANG Li. Recent research on cytokines associated with anti-N-methyl-D-aspartate receptor encephalitis[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(3): 321-327 https://doi.org/10.7499/j.issn.1008-8830.2211125

参考文献

1 Dalmau J, Armangué T, Planagumà J, et al. An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models[J]. Lancet Neurol, 2019, 18(11): 1045-1057. PMID: 31326280. DOI: 10.1016/S1474-4422(19)30244-3.
2 Li X, Hou C, Wu WL, et al. Pediatric anti-N-methyl-d-aspartate receptor encephalitis in southern China: analysis of 111 cases[J]. J Neuroimmunol, 2021, 352: 577479. PMID: 33486307. DOI: 10.1016/j.jneuroim.2021.577479.
3 Xu X, Lu Q, Huang Y, et al. Anti-NMDAR encephalitis: a single-center, longitudinal study in China[J]. Neurol Neuroimmunol Neuroinflamm, 2020, 7(1): e633. PMID: 31619447. PMCID: PMC6857906. DOI: 10.1212/NXI.0000000000000633.
4 Traynelis SF, Wollmuth LP, McBain CJ, et al. Glutamate receptor ion channels: structure, regulation, and function[J]. Pharmacol Rev, 2010, 62(3): 405-496. PMID: 20716669. PMCID: PMC2964903. DOI: 10.1124/pr.109.002451.
5 Bost C, Chanson E, Picard G, et al. Malignant tumors in autoimmune encephalitis with anti-NMDA receptor antibodies[J]. J Neurol, 2018, 265(10): 2190-2200. PMID: 30003358. DOI: 10.1007/s00415-018-8970-0.
6 Armangue T, Spatola M, Vlagea A, et al. Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis[J]. Lancet Neurol, 2018, 17(9): 760-772. PMID: 30049614. PMCID: PMC6128696. DOI: 10.1016/S1474-4422(18)30244-8.
7 Dalmau J. NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: the 2016 Cotzias lecture[J]. Neurology, 2016, 87(23): 2471-2482. PMID: 27920282. PMCID: PMC5177671. DOI: 10.1212/WNL.0000000000003414.
8 Hughes EG, Peng X, Gleichman AJ, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis[J]. J Neurosci, 2010, 30(17): 5866-5875. PMID: 20427647. PMCID: PMC2868315. DOI: 10.1523/JNEUROSCI.0167-10.2010.
9 Zrzavy T, Endmayr V, Bauer J, et al. Neuropathological variability within a spectrum of NMDAR-encephalitis[J]. Ann Neurol, 2021, 90(5): 725-737. PMID: 34562035. DOI: 10.1002/ana.26223.
10 Wagnon I, Hélie P, Bardou I, et al. Autoimmune encephalitis mediated by B-cell response against N-methyl-d-aspartate receptor[J]. Brain, 2020, 143(10): 2957-2972. PMID: 32893288. DOI: 10.1093/brain/awaa250.
11 Chetaille Nézondet AL, Poubelle PE, Pelletier M. The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases[J]. J Leukoc Biol, 2020, 108(2): 647-657. PMID: 32040246. DOI: 10.1002/JLB.5MR0120-218RRR.
12 Pan Z, Zhu T, Liu Y, et al. Role of the CXCL13/CXCR5 axis in autoimmune diseases[J]. Front Immunol, 2022, 13: 850998. PMID: 35309354. PMCID: PMC8931035. DOI: 10.3389/fimmu.2022.850998.
13 Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease[J]. Cold Spring Harb Perspect Biol, 2014, 6(10): a016295. PMID: 25190079. PMCID: PMC4176007. DOI: 10.1101/cshperspect.a016295.
14 Alawdi SH, El-Denshary ES, Safar MM, et al. Neuroprotective effect of nanodiamond in Alzheimer's disease rat model: a pivotal role for modulating NF-κB and STAT3 signaling[J]. Mol Neurobiol, 2017, 54(3): 1906-1918. PMID: 26897372. DOI: 10.1007/s12035-016-9762-0.
15 Haramati A, Rechtman A, Zveik O, et al. IL-6 as a marker for NMOSD disease activity[J]. J Neuroimmunol, 2022, 370: 577925. PMID: 35810527. DOI: 10.1016/j.jneuroim.2022.577925.
16 Li Q, Chen J, Yin M, et al. High level of soluble CD146 in cerebrospinal fluid might be a biomarker of severity of anti-N-methyl-D-Aspartate receptor encephalitis[J]. Front Immunol, 2021, 12: 680424. PMID: 34220828. PMCID: PMC8245058. DOI: 10.3389/fimmu.2021.680424.
17 Liu J, Liu L, Kang W, et al. Cytokines/chemokines: potential biomarkers for non-paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis[J]. Front Neurol, 2020, 11: 582296. PMID: 33408682. PMCID: PMC7779630. DOI: 10.3389/fneur.2020.582296.
18 Wang X, Ma C, Liu CY, et al. Neuronal NMDAR currents of the hippocampus and learning performance in autoimmune anti-NMDAR encephalitis and involvement of TNF-α and IL-6[J]. Front Neurol, 2019, 10: 684. PMID: 31297084. PMCID: PMC6607466. DOI: 10.3389/fneur.2019.00684.
19 Lee WJ, Lee ST, Shin YW, et al. Teratoma removal, steroid, IVIG, rituximab and tocilizumab (T-SIRT) in anti-NMDAR encephalitis[J]. Neurotherapeutics, 2021, 18(1): 474-487. PMID: 32880854. PMCID: PMC8116457. DOI: 10.1007/s13311-020-00921-7.
20 Veldhoen M. Interleukin 17 is a chief orchestrator of immunity[J]. Nat Immunol, 2017, 18(6): 612-621. PMID: 28518156. DOI: 10.1038/ni.3742.
21 Regen T, Isaac S, Amorim A, et al. IL-17 controls central nervous system autoimmunity through the intestinal microbiome[J]. Sci Immunol, 2021, 6(56): eaaz6563. PMID: 33547052. DOI: 10.1126/sciimmunol.aaz6563.
22 Zeng C, Chen L, Chen B, et al. Th17 cells were recruited and accumulated in the cerebrospinal fluid and correlated with the poor prognosis of anti-NMDAR encephalitis[J]. Acta Biochim Biophys Sin (Shanghai), 2018, 50(12): 1266-1273. PMID: 30418472. DOI: 10.1093/abbs/gmy137.
23 Peng Y, Liu B, Pei S, et al. Higher CSF levels of NLRP3 inflammasome is associated with poor prognosis of anti-N-methyl-D-aspartate receptor encephalitis[J]. Front Immunol, 2019, 10: 905. PMID: 31214158. PMCID: PMC6554706. DOI: 10.3389/fimmu.2019.00905.
24 Balasa R, Bianca C, Septimiu V, et al. The matrix metalloproteinases panel in multiple sclerosis patients treated with natalizumab: a possible answer to natalizumab non- responders[J]. CNS Neurol Disord Drug Targets, 2018, 17(6): 464-472. PMID: 29968546. DOI: 10.2174/1871527317666180703102536.
25 Reich K, Warren RB, Lebwohl M, et al. Bimekizumab versus secukinumab in Plaque Psoriasis[J]. N Engl J Med, 2021, 385(2): 142-152. PMID: 33891380. DOI: 10.1056/NEJMoa2102383.
26 Murray PJ. Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response[J]. Curr Opin Pharmacol, 2006, 6(4): 379-386. PMID: 16713356. DOI: 10.1016/j.coph.2006.01.010.
27 Mege JL, Meghari S, Honstettre A, et al. The two faces of interleukin 10 in human infectious diseases[J]. Lancet Infect Dis, 2006, 6(9): 557-569. PMID: 16931407. DOI: 10.1016/S1473-3099(06)70577-1.
28 Xin G, Zander R, Schauder DM, et al. Single-cell RNA sequencing unveils an IL-10-producing helper subset that sustains humoral immunity during persistent infection[J]. Nat Commun, 2018, 9(1): 5037. PMID: 30487586. PMCID: PMC6261948. DOI: 10.1038/s41467-018-07492-4.
29 Qiao J, Liu Z, Dong C, et al. Targeting tumors with IL-10 prevents dendritic cell-mediated CD8+ T cell apoptosis[J]. Cancer Cell, 2019, 35(6): 901-915.e4. PMID: 31185213. DOI: 10.1016/j.ccell.2019.05.005.
30 Yogev N, Bedke T, Kobayashi Y, et al. CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival[J]. Cell Rep, 2022, 38(13): 110565. PMID: 35354043. DOI: 10.1016/j.celrep.2022.110565.
31 Peng Y, Zheng D, Zhang X, et al. Cell-Free mitochondrial DNA in the CSF: a potential prognostic biomarker of anti-NMDAR encephalitis[J]. Front Immunol, 2019, 10: 103. PMID: 30792710. PMCID: PMC6375341. DOI: 10.3389/fimmu.2019.00103.
32 Sáez de Guinoa J, Barrio L, Mellado M, et al. CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics[J]. Blood, 2011, 118(6): 1560-1569. PMID: 21659539. DOI: 10.1182/blood-2011-01-332106.
33 Harrer C, Otto F, Pilz G, et al. The CXCL13/CXCR5-chemokine axis in neuroinflammation: evidence of CXCR5+CD4 T cell recruitment to CSF[J]. Fluids Barriers CNS, 2021, 18(1): 40. PMID: 34446066. PMCID: PMC8390062. DOI: 10.1186/s12987-021-00272-1.
34 Eckman EA, Clausen DM, Herdt AR, et al. Specificity and diagnostic utility of cerebrospinal fluid CXCL13 in Lyme neuroborreliosis[J]. Clin Infect Dis, 2021, 72(10): 1719-1726. PMID: 32221538. DOI: 10.1093/cid/ciaa335.
35 Barstad B, Henningsson AJ, Tveitnes D, et al. Cerebrospinal fluid cytokines and chemokines in children with Lyme neuroborreliosis; pattern and diagnostic utility[J]. Cytokine, 2020, 130: 155023. PMID: 32199247. DOI: 10.1016/j.cyto.2020.155023.
36 Lucchini M, De Arcangelis V, Piro G, et al. CSF CXCL13 and chitinase 3-like-1 levels predict disease course in relapsing multiple sclerosis[J]. Mol Neurobiol, 2023, 60(1): 36-50. PMID: 36215027. PMCID: PMC9758105. DOI: 10.1007/s12035-022-03060-6.
37 Li Y, Yang K, Zhang F, et al. Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: high-throughput proteomic investigation[J]. Front Immunol, 2022, 13: 971659. PMID: 36389787. PMCID: PMC9643472. DOI: 10.3389/fimmu.2022.971659.
38 Leypoldt F, H?ftberger R, Titulaer MJ, et al. Investigations on CXCL13 in anti-N-methyl-D-aspartate receptor encephalitis: a potential biomarker of treatment response[J]. JAMA Neurol, 2015, 72(2): 180-186. PMID: 25436993. PMCID: PMC4836910. DOI: 10.1001/jamaneurol.2014.2956.
39 Kothur K, Wienholt L, Mohammad SS, et al. Utility of CSF cytokine/chemokines as markers of active intrathecal inflammation: comparison of demyelinating, anti-NMDAR and enteroviral encephalitis[J]. PLoS One, 2016, 11(8): e0161656. PMID: 27575749. PMCID: PMC5004915. DOI: 10.1371/journal.pone.0161656.
40 Liu B, Liu J, Sun H, et al. Autoimmune encephalitis after Japanese encephalitis in children: a prospective study[J]. J Neurol Sci, 2021, 424: 117394. PMID: 33773410. DOI: 10.1016/j.jns.2021.117394.
41 Pilz G, Sakic I, Wipfler P, et al. Chemokine CXCL13 in serum, CSF and blood—CSF barrier function: evidence of compartment restriction[J]. Fluids Barriers CNS, 2020, 17(1): 7. PMID: 32089130. PMCID: PMC7038591. DOI: 10.1186/s12987-020-0170-5.
42 Dai S, Liu F, Qin Z, et al. Kupffer cells promote T-cell hepatitis by producing CXCL10 and limiting liver sinusoidal endothelial cell permeability[J]. Theranostics, 2020, 10(16): 7163-7177. PMID: 32641985. PMCID: PMC7330839. DOI: 10.7150/thno.44960.
43 Nohejlova H, Kayserova J, Capek V, et al. Paediatric onset of multiple sclerosis: analysis of chemokine and cytokine levels in the context of the early clinical course[J]. Mult Scler Relat Disord, 2020, 46: 102467. PMID: 32889374. DOI: 10.1016/j.msard.2020.102467.
44 吕遐, 徐晓璐, 任海涛, 等. 抗N-甲基-D-天冬氨酸受体脑炎患者细胞因子检测及其临床意义[J]. 中国神经免疫学和神经病学杂志, 2021, 28(3): 214-218, 223. DOI: 10.3969/j.issn.1006-2963.2021.03.009.
45 Shaul ME, Zlotnik A, Tidhar E, et al. Tumor-associated neutrophils drive B-cell recruitment and their differentiation to plasma cells[J]. Cancer Immunol Res, 2021, 9(7): 811-824. PMID: 33906865. DOI: 10.1158/2326-6066.CIR-20-0839.
46 Smulski CR, Zhang L, Burek M, et al. Ligand-independent oligomerization of TACI is controlled by the transmembrane domain and regulates proliferation of activated B cells[J]. Cell Rep, 2022, 38(13): 110583. PMID: 35354034. DOI: 10.1016/j.celrep.2022.110583.
47 Vincent FB, Saulep-Easton D, Figgett WA, et al. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity[J]. Cytokine Growth Factor Rev, 2013, 24(3): 203-215. PMID: 23684423. PMCID: PMC7108297. DOI: 10.1016/j.cytogfr.2013.04.003.
48 Baert L, Benkhoucha M, Popa N, et al. A proliferation-inducing ligand-mediated anti-inflammatory response of astrocytes in multiple sclerosis[J]. Ann Neurol, 2019, 85(3): 406-420. PMID: 30635946. DOI: 10.1002/ana.25415.
49 Lim KH, Chen LC, Hsu K, et al. BAFF-driven NLRP3 inflammasome activation in B cells[J]. Cell Death Dis, 2020, 11(9): 820. PMID: 33004801. PMCID: PMC7529748. DOI: 10.1038/s41419-020-03035-2.
50 Deng B, Liu XN, Li X, et al. Raised cerebrospinal fluid BAFF and APRIL levels in anti-N-methyl-d-aspartate receptor encephalitis: correlation with clinical outcome[J]. J Neuroimmunol, 2017, 305: 84-91. PMID: 28284352. DOI: 10.1016/j.jneuroim.2017.01.012.
51 Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis[J]. N Engl J Med, 2020, 383(12): 1117-1128. PMID: 32937045. DOI: 10.1056/NEJMoa2001180.