脑脊液与血清免疫球蛋白在抗NMDAR脑炎与抗LGI1抗体相关脑炎鉴别诊断中的临床价值

doi:10.3969/j.issn.1004-583X.2026.08.007

摘要/Abstract

摘要：

目的分析抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor, NMDAR)脑炎和抗富亮氨酸胶质瘤失活蛋白1(leucine-rich glioma inactivated protein 1, LGI1)抗体相关脑炎患者脑脊液免疫球蛋白与血清免疫球蛋白特点,以及各组脑脊液免疫球蛋白和血清免疫球蛋白的相关性,探讨临床应用价值。方法选取2019年1月-2024年1月天津市环湖医院收治的抗NMDAR脑炎患者30例(抗 NMDAR脑炎组)和抗LGI1抗体相关脑炎患者21例(抗LGI1抗体相关脑炎组)。测定两组脑脊液免疫球蛋白G(immunoglobulin G, IgG)、免疫球蛋白A(immunoglobulin A, IgA)、免疫球蛋白M(immunoglobulin M, IgM)及血清免疫球蛋白(IgG、IgA、IgM)浓度,比较两组脑脊液及血清免疫球蛋白水平,并探究各组脑脊液免疫球蛋白与血清免疫球蛋白的相关性。结果抗NMDAR脑炎组与抗LGI1抗体相关脑炎组脑脊液及血清IgG、IgA差异均无统计学意义(P>0.05),而抗NMDAR脑炎组脑脊液及血清IgM均明显高于抗LGI1抗体相关脑炎组,差异有统计学意义(P<0.05)。抗NMDAR脑炎组脑脊液IgA与血清IgA呈正相关(P<0.05),脑脊液IgM与血清IgM呈正相关(P<0.05)。抗LGI1抗体相关脑炎组脑脊液IgG与血清IgG呈正相关(P<0.05),脑脊液IgA与血清IgA呈正相关(P<0.05)。结论脑脊液与血清免疫球蛋白水平可为临床鉴别抗NMDAR脑炎及抗LGI1抗体相关脑炎提供辅助参考。抗NMDAR脑炎组与抗LGI1抗体相关脑炎组脑脊液与血清免疫球蛋白相关性的差异,提示两组血脑屏障破坏程度可能存在异质性,且可能涉及不同的病理生理机制。

关键词: 抗N-甲基-D-门冬氨酸受体脑炎, 抗富亮氨酸胶质瘤失活蛋白1抗体相关脑炎, 血清免疫球蛋白, 脑脊液免疫球蛋白

Abstract:

Objective To analyze the characteristics of cerebrospinal fluid (CSF) and serum immunoglobulins in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis and anti-leucine-rich glioma inactivated protein 1 (LGI1) antibody-associated encephalitis, as well as the correlations between CSF and serum immunoglobulins in each group, and to explore their clinical value. Methods A total of 30 patients with anti-NMDAR encephalitis (anti-NMDAR encephalitis group) and 21 patients with anti-LGI1 antibody-associated encephalitis (anti-LGI1 antibody-associated encephalitis group) admitted to Tianjin Huanhu Hospital from January 2019 to January 2024 were selected. The concentrations of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in CSF, as well as serum immunoglobulins (IgG, IgA, and IgM), were measured. CSF and serum immunoglobulin levels were compared between the two groups, and the correlations between CSF and serum immunoglobulins were analyzed in each group. Results There were no statistically significant differences in CSF or serum IgG and IgA between the anti-NMDAR encephalitis group and the anti-LGI1 antibody-associated encephalitis group (P>0.05). However, both CSF and serum IgM levels were significantly higher in the anti-NMDAR encephalitis group than in the anti-LGI1 antibody-associated encephalitis group (P<0.05). In the anti-NMDAR encephalitis group, CSF IgA was positively correlated with serum IgA (P<0.05), and CSF IgM was positively correlated with serum IgM (P<0.05). In the anti-LGI1 antibody-associated encephalitis group, CSF IgG was positively correlated with serum IgG (P<0.05), and CSF IgA was positively correlated with serum IgA (P<0.05).Conclusion CSF and serum immunoglobulin levels may provide an auxiliary reference for the clinical differentiation of anti-NMDAR encephalitis and anti-LGI1 antibody-associated encephalitis. Differences in the correlations between CSF and serum immunoglobulins in the two groups suggest possible heterogeneity in blood-brain barrier disruption and may involve different pathophysiological mechanisms.

Key words: anti-N-methyl-D-aspartic acid receptor encephalitis, anti-leucine-rich glioma inactivated protein 1 antibody-associated encephalitis, serum immunoglobulin, cerebrospinal fluid immunoglobulin

中图分类号:

R741

郑新伟. 脑脊液与血清免疫球蛋白在抗NMDAR脑炎与抗LGI1抗体相关脑炎鉴别诊断中的临床价值[J]. 临床荟萃, 2026, 41(8): 711-715.

Zheng Xinwei. Clinical value of cerebrospinal fluid and serum immunoglobulins in the differential diagnosis of anti-NMDAR encephalitis and anti-LGI1 antibody-associated encephalitis[J]. Clinical Focus, 2026, 41(8): 711-715.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.08.007

https://www.lchc.cn/CN/Y2026/V41/I8/711

图/表 4

参考文献 24

[1]	Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: A multicentre, population-based prospective study[J]. Lancet Infect Dis, 2010, 10(12):835-844. doi: 10.1016/S1473-3099(10)70222-X. pmid: 20952256
[2]	Van Sonderen A, Schreurs MW, Wirtz PW, et al. From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over time[J]. Autoimmun Rev, 2016, 15(10):970-974. doi: 10.1016/j.autrev.2016.07.018. pmid: 27485013
[3]	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. doi: 10.1016/S1474-4422(19)30244-3. pmid: 31326280
[4]	Uy CE, Binks S, Irani SR. Autoimmune encephalitis: Clinical spectrum and management[J]. Pract Neurol, 2021, 21(5):412-423.doi:10.1136/practneurol-2020-002567. pmid: 34108243
[5]	Dalmau J, Graus F. Antibody-mediated encephalitis[J]. N Engl J Med, 2018, 378(9):840-851. doi: 10.1056/NEJMra1708712.
[6]	Van Sonderen A, Petit-Pedrol M, Dalmau J, et al. The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis[J]. Nat Rev Neurol, 2017, 13(5):290-301. doi: 10.1038/nrneurol.2017.43. pmid: 28418022
[7]	Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis[J]. Lancet Neurol, 2016, 15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. pmid: 26906964
[8]	Van Sonderen A, Thijs RD, Coenders EC, et al. Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up[J]. Neurology, 2016, 87(14):1449-1456. doi: 10.1212/WNL.0000000000003173. pmid: 27590293
[9]	Ariño H, Armangué T, Petit-Pedrol M, et al. Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome[J]. Neurology, 2016, 87(8):759-765. doi: 10.1212/WNL.0000000000003009. pmid: 27466467
[10]	Irani SR, Bera K, Waters P, et al. N-methyl-D-aspartate antibody encephalitis: Temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes[J]. Brain, 2010, 133(Pt 6):1655-1667. doi: 10.1093/brain/awq113. pmid: 20511282
[11]	Zrzavy T, Höftberger R, Wimmer I, et al. Longitudinal CSF findings in autoimmune encephalitis-A monocentric cohort study[J]. Front Immunol, 2021, 12:646940.doi: 10.3389/fimmu.2021.646940.
[12]	Räuber S, Schroeter CB, Strippel C, et al. Cerebrospinal fluid proteomics indicates immune dysregulation and neuronal dysfunction in antibody associated autoimmune encephalitis[J]. J Autoimmun, 2023, 135:102985. doi: 10.1016/j.jaut.2022.102985.
[13]	中华医学会神经病学分会. 中国自身免疫性脑炎诊治专家共识[J]. 中华神经科杂志, 2017, 50(2):91-98.doi: 10.3760/cma.j.issn.1006-7876.2017.02.004.
[14]	Bien CG, Bien CI, Dogan Onugoren M, et al. Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome[J]. J Neurol, 2020, 267(7):2115-2116. doi: 10.1007/s00415-020-09855-8. pmid: 32399693
[15]	Davis AG, Rohlwink UK, Proust A, et al. The pathogenesis of tuberculous meningitis[J]. J Leukoc Biol, 2019, 105(2):267-280. doi: 10.1002/JLB.MR0318-102R.
[16]	He H, Xu J, Peng Q, et al. The application value of cerebrospinal fluid immunoglobulin in tuberculous meningitis[J]. Microbiol Spectr, 2024, 12(6):e0015724. doi: 10.1128/spectrum.00157-24.
[17]	Karrenbauer VD, Bedri SK, Hillert J, et al. Cerebrospinal fluid oligoclonal immunoglobulin gamma bands and long-term disability progression in multiple sclerosis: A retrospective cohort study[J]. Sci Rep, 2021, 11(1):14987. doi: 10.1038/s41598-021-94423-x. pmid: 34294805
[18]	Hu X, Cheng S. The role of immunoglobulin in cerebrospinal fluid on the differential diagnosis of autoimmune encephalitis and viral encephalitis in children[J]. BMC Pediatr, 2024, 24(1):386. doi: 10.1186/s12887-024-04824-w. pmid: 38851704
[19]	Huang JY, Fan WX, Meng J, et al. Immune characteristics of children with autoimmune encephalitis and the correlation with a short-term prognosis[J]. Ital J Pediatr, 2022, 48(1):94. doi: 10.1186/s13052-022-01247-0.
[20]	Dürr M, Nissen G, Sühs KW, et al. CSF findings in acute NMDAR and LGI1 antibody-associated autoimmune encephalitis[J]. Neurol Neuroimmunol Neuroinflamm, 2021, 8(6):e1086. doi: 10.1212/NXI.0000000000001086.
[21]	Schreiner TG, Romanescu C, Popescu BO. The blood-brain barrier-a key player in multiple sclerosis disease mechanisms[J]. Biomolecules, 2022, 12(4):538. doi: 10.3390/biom12040538.
[22]	Yu Y, Wu Y, Cao X, et al. The clinical features and prognosis of anti-NMDAR encephalitis depends on blood brain barrier integrity[J]. Mult Scler Relat Disord, 2021, 47:102604. doi: 10.1016/j.msard.2020.102604.
[23]	Mao F, Huang F, Nong W, et al. N-methyl-D-aspartic acid increases tight junction protein destruction in brain endothelial cell via caveolin-1-associated ERK1/2 signaling[J]. Toxicology, 2022, 470:153139. doi: 10.1016/j.tox.2022.153139.
[24]	Tröscher AR, Klang A, French M, et al. Selective limbic blood-brain barrier breakdown in a feline model of limbic encephalitis with LGI1 antibodies[J]. Front Immunol, 2017, 8:1364. doi: 10.3389/fimmu.2017.01364. pmid: 29093718

组别	例数	脑脊液IgG(mg/L)	脑脊液IgA(mg/L)	脑脊液IgM(mg/L)
抗NMDAR脑炎组	30	46.00(28.97, 65.40)	4.63(3.09, 6.81)	0.66(0.32, 1.56)
抗LGI1抗体相关脑炎组	21	43.00(28.35, 61.20)	4.19(2.76, 6.93)	0.35(0.23, 0.70)
Z值		-0.555	-0.268	-2.115
P值		0.579	0.789	0.034

组别	例数	脑脊液IgG(mg/L)	脑脊液IgA(mg/L)	脑脊液IgM(mg/L)
抗NMDAR脑炎组	30	46.00(28.97, 65.40)	4.63(3.09, 6.81)	0.66(0.32, 1.56)
抗LGI1抗体相关脑炎组	21	43.00(28.35, 61.20)	4.19(2.76, 6.93)	0.35(0.23, 0.70)
Z值		-0.555	-0.268	-2.115
P值		0.579	0.789	0.034

组别	例数	血清IgG(g/L)	血清IgA(g/L)	血清IgM(g/L)
抗NMDAR脑炎组	30	11.40(10.02, 15.10)	2.18(1.56, 3.02)	0.88(0.61, 1.11)
抗LGI1抗体相关脑炎组	21	11.40(9.38, 14.10)	2.40(1.71, 2.85)	0.66(0.38, 0.90)
Z值		-0.469	-0.727	-2.067
P值		0.639	0.467	0.039

组别	例数	血清IgG(g/L)	血清IgA(g/L)	血清IgM(g/L)
抗NMDAR脑炎组	30	11.40(10.02, 15.10)	2.18(1.56, 3.02)	0.88(0.61, 1.11)
抗LGI1抗体相关脑炎组	21	11.40(9.38, 14.10)	2.40(1.71, 2.85)	0.66(0.38, 0.90)
Z值		-0.469	-0.727	-2.067
P值		0.639	0.467	0.039

项目	脑脊液IgG		脑脊液IgA		脑脊液IgM
项目	r_s值	P值	r_s值	P值	r_s值	P值
血清IgG	-0.052	0.783	-0.284	0.129	0.053	0.780
血清IgA	-0.276	0.140	0.406	0.026	-0.064	0.738
血清IgM	0.159	0.402	0.170	0.369	0.678	0.000