Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Autoantibody Screening and Purification
2.2. Epitope Determination
2.3. Determination of IgG Subclasses of Anti-LGI1 ab Fractions and Purification
2.4. HLA-Mapping
2.5. Isolation of IgG Fractions
2.6. Electrophysiology
2.7. Slice Preparation
2.8. Imaging and Analysis of Spine Density in Hippocampal Slices
2.9. Immunohistochemistry/Cluster Differentiation
2.10. Data Analysis and Statistics
3. Results
3.1. Patients Description
3.2. IgG Subclass Analysis and Epitope Mapping Reveal Differences between Patients with LE and FBDS
3.3. Electrophysiological Effects of LGI1 abs Differ between Patients with FBDS and the Patients with LE
3.4. Hippocampal Spine Density Is Reduced by IgG from the Patients with LE Compared to IgG from Patients with FBDS
3.5. No Significant Changes of Postsynaptic AMPA-R Density Observed in Slices after Treatment with LGI1 ab from Patient LE#1, but Increased Cell Apoptosis after LGI1 ab Treatment from Patient LE#2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Recorded data | Variable | LE #1 | LE #2 | FBDS #1 | FBDS #2 |
---|---|---|---|---|---|
Symptoms | Limbic encephalitis | Limbic encephalitis | FBDS, complex partial sz. | FBDS | |
LGI1 titre | initial | 1:100 | 1:20 | 1:1000 | 1:160 |
after treament | 1:30 | none | 1:100 | 1:10 | |
Treatment | MP, PLEX, Rit. | MP, Rit. | MP, PLEX, Rit. | MP | |
Epitopes | KKPAK, HTFR, CEGPP, | GTSVVC, AQPFTGKCIF, VEKTFRNYDN | NDEYV, VEYL | ISEGSF, ISDO, CIITE, LND, PIVIET, VEY | |
HLA Type | DRB1*04:02[DR4]; DQA1*03:01;DQB1*03:02[DQ8(3);DPA1*01:03;DPA1*02:01,DPB1*01:01[DPw1],DPB1*04:01[DPw4] | DRB1*07:01[DR7],DQA1*02:01,DQB1*02:02[DQ2],DRB1*08:01[DR8], DQA1*04:01, DQB1*04:02[DQ4 | DRB1*04[DR4],DQA1*03,DRB1*07[DR7],DQB1*02:02[DQ2],DQB1*03:02[DQ8(3),DPA1*01:03,DPA1*02:01,DPB1*02:01[DPw2],DPB1*04:01[DPw4] | DRB1*04:07[DR4],DQA1*02:01; DQB1*02:02[DQ2],DQB1*03:01[DQ7(3)],DRB1*01[DR7 | |
Electrophysiology | LTP mean of averaged potentiation values (%) | Patient 1: 134.32% ± 3.92; Control: 128.06% ± 3.31 | Patient 2: 118.88% ± 3.35; Control: 120.81% ± 3.63 | Patient 3: 123.36% ± 3.37; Control: 124.80% ± 4.80 | Patient 4: 132.9% ± 3.6; Control: 134.4% ± 8.4 |
1 h incubation | N = 13, n = 27 | N = 6, n = 12 | N = 11, n = 19 | N = 10, n = 18 | |
p = 0.419 | p = 0.876 | p = 0.706 | p = 0.810 | ||
6 h incubation | Patient 1: 111.67% ± 4.07; Control: 126.29% ± 3.94 | Patient 2: 118.30% ± 3.92; Control: 115.34% ± 2.75 | Patient 3: 115.38% ± 2.33; Control: 115.4% 8 ± 2.45 | Patient 4: 120.3% ± 7.2; Control: 125.6% ± 6.9 | |
N = 13, n = 31 | N = 6, n = 10 | N = 10, n = 23 | N = 8, n = 21 | ||
p = 0.015 | p = 0.601 | p = 0.451 | p = 0.978 | ||
Spine density | spine density | Patient 1: 1.91 ± 0.05; Control: 1.95 ± 0.05 spines/µm dendrite | Patient 2: 2.04 ± 0.06; Control: 1.96 ± 0.06 spines/µm dendrite | Patient 3: 1.86 ± 0.04; Control: 1.87 ± 0.03 spines/µm dendrite | Patient 4: 2.19 ± 0.04; Control: 2.18 ± 0.04 spines/µm dendrite |
CA1 apical | 1 h incubation | N = 3, n = 15 | N = 3, n = 15 | N = 3, n = 15 | N = 3, n = 15 |
3086 spines | 5365 spines | 3258 spines | 2738 spines | ||
p = 0.548 | p = 0.9013 | p = 0.393 | p = 0.202 | ||
6 h incubation | Patient 1: 1.84 ± 0.04; Control: 1.78 ± 0.04 spines/µm dendrite | Patient 2: 2.00 ± 0.03; Control: 1.96 ± 0.04 spines/µm dendrite | Patient 3: 1.80 ± 0.04; Control: 1.87 ± 0.03 spines/µm dendrite | Patient 4: 2.07 ± 0.03; Control: 2.19 ± 0.03 spines/µm dendrite | |
N = 3, n = 15 | N = 3, n = 15 | N = 3, n = 15 | N = 3, n = 15 | ||
3128 spines | 4705 spines | 3152 spines | 3067 spines | ||
p = 0.345 | p = 0.0152 | p = 0.414 | p = 0.147 | ||
Dentate Gyrus | 6 h incubation | Patient 1: 1.73 ± 0.05; Control: 1.89 ± 0.03 spines/µm dendrite | Patient 2: 2.23 ± 0.07; Control: 2.19 ± 0.07 spines/µm dendrite | Patient 3: 2.00 ± 0.05; Control: 1.96 ± 0.06 spines/µm dendrite | Patient 4: 2.08 ± 0.05; Control: 1.25 ± 0.03 spines/µm dendrite |
N = 3, n = 15 | N = 3, n = 15 | N = 3, n = 15 | N= 3, n = 15 | ||
3137 spines | 2819 | 3489 | 3310 | ||
p= 0.014 | p < 0.0001 | p = 0.630 | p = 0.705 |
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Ludewig, S.; Salzburger, L.; Goihl, A.; Rohne, J.; Leypoldt, F.; Bittner, D.; Düzel, E.; Schraven, B.; Reinhold, D.; Korte, M.; et al. Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis. Cells 2023, 12, 282. https://doi.org/10.3390/cells12020282
Ludewig S, Salzburger L, Goihl A, Rohne J, Leypoldt F, Bittner D, Düzel E, Schraven B, Reinhold D, Korte M, et al. Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis. Cells. 2023; 12(2):282. https://doi.org/10.3390/cells12020282
Chicago/Turabian StyleLudewig, Susann, Leonie Salzburger, Alexander Goihl, Jana Rohne, Frank Leypoldt, Daniel Bittner, Emrah Düzel, Burkhart Schraven, Dirk Reinhold, Martin Korte, and et al. 2023. "Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis" Cells 12, no. 2: 282. https://doi.org/10.3390/cells12020282
APA StyleLudewig, S., Salzburger, L., Goihl, A., Rohne, J., Leypoldt, F., Bittner, D., Düzel, E., Schraven, B., Reinhold, D., Korte, M., & Körtvélyessy, P. (2023). Antibody Properties Associate with Clinical Phenotype in LGI1 Encephalitis. Cells, 12(2), 282. https://doi.org/10.3390/cells12020282