New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.
Autoimmunity
Autopsies
Biopsies
GFAP
Magnetic resonance imaging
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
03 Feb 2024
03 Feb 2024
Historique:
received:
05
09
2023
accepted:
24
12
2023
revised:
06
12
2023
medline:
4
2
2024
pubmed:
4
2
2024
entrez:
3
2
2024
Statut:
epublish
Résumé
Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8
Identifiants
pubmed: 38310187
doi: 10.1007/s00401-023-02678-7
pii: 10.1007/s00401-023-02678-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
31Subventions
Organisme : Austrian Science Fund
ID : I6565-B
Informations de copyright
© 2024. The Author(s).
Références
Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J et al (2021) A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature 597:709–714. https://doi.org/10.1038/s41586-021-03892-7
doi: 10.1038/s41586-021-03892-7
pubmed: 34497421
pmcid: 8719282
Bankhead P, Loughrey MB, Fernandez JA, Dombrowski Y, McArt DG, Dunne PD et al (2017) QuPath: Open source software for digital pathology image analysis. Sci Rep 7:16878. https://doi.org/10.1038/s41598-017-17204-5
doi: 10.1038/s41598-017-17204-5
pubmed: 29203879
pmcid: 5715110
Barber RM, Schatzberg SJ, Corneveaux JJ, Allen AN, Porter BF, Pruzin JJ et al (2011) Identification of risk loci for necrotizing meningoencephalitis in Pug dogs. J Hered 102(Suppl 1):S40-46. https://doi.org/10.1093/jhered/esr048
doi: 10.1093/jhered/esr048
pubmed: 21846746
Battin C, De Sousa LA, Paster W, Isenman DE, Wahrmann M, Leitner J et al (2019) Neuropilin-1 acts as a receptor for complement split products. Front Immunol 10:2209. https://doi.org/10.3389/fimmu.2019.02209
doi: 10.3389/fimmu.2019.02209
pubmed: 31572401
pmcid: 6753332
Cabarrocas J, Bauer J, Piaggio E, Liblau R, Lassmann H (2003) Effective and selective immune surveillance of the brain by MHC class I-restricted cytotoxic T lymphocytes. Eur J Immunol 33:1174–1182. https://doi.org/10.1002/eji.200323492
doi: 10.1002/eji.200323492
pubmed: 12731042
Cohen D, Colvin RB, Daha MR, Drachenberg CB, Haas M, Nickeleit V et al (2012) Pros and cons for C4d as a biomarker. Kidney Int 81:628–639. https://doi.org/10.1038/ki.2011.497
doi: 10.1038/ki.2011.497
pubmed: 22297669
pmcid: 3771104
Daugan MV, Revel M, Russick J, Dragon-Durey MA, Gaboriaud C, Robe-Rybkine T et al (2021) Complement C1s and C4d as prognostic biomarkers in renal cancer: emergence of noncanonical functions of C1s. Cancer Immunol Res 9:891–908. https://doi.org/10.1158/2326-6066.CIR-20-0532
doi: 10.1158/2326-6066.CIR-20-0532
pubmed: 34039653
Dubey D, Hinson SR, Jolliffe EA, Zekeridou A, Flanagan EP, Pittock SJ et al (2018) Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1year. J Neuroimmunol 321:157–163. https://doi.org/10.1016/j.jneuroim.2018.04.016
doi: 10.1016/j.jneuroim.2018.04.016
pubmed: 29793728
Dumonceau AG, Ameli R, Rogemond V, Ruiz A, Joubert B, Muniz-Castrillo S et al (2021) Glial fibrillary acidic protein autoimmunity: a French cohort study. Neurology. https://doi.org/10.1212/WNL.0000000000013087
doi: 10.1212/WNL.0000000000013087
Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ et al (2016) Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 73:1297–1307. https://doi.org/10.1001/jamaneurol.2016.2549
doi: 10.1001/jamaneurol.2016.2549
pubmed: 27618707
Fang J, Tong Z, Lu W (2022) Case report: need for caution in the diagnosis of GFAP astrocytopathy—A case of GFAP astrocytopathy coexistent with primary central nervous system lymphoma. Front Neurol 13:806224. https://doi.org/10.3389/fneur.2022.806224
doi: 10.3389/fneur.2022.806224
pubmed: 35153997
pmcid: 8831885
Flanagan EP, Hinson SR, Lennon VA, Fang B, Aksamit AJ, Morris PP et al (2017) Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol 81:298–309. https://doi.org/10.1002/ana.24881
doi: 10.1002/ana.24881
pubmed: 28120349
Gravier-Dumonceau A, Ameli R, Rogemond V, Ruiz A, Joubert B, Muniz-Castrillo S et al (2022) Glial fibrillary acidic protein autoimmunity: a French cohort study. Neurology 98:e653–e668. https://doi.org/10.1212/WNL.0000000000013087
doi: 10.1212/WNL.0000000000013087
pubmed: 34799461
pmcid: 8829963
Greer KA, Schatzberg SJ, Porter BF, Jones KA, Famula TR, Murphy KE (2009) Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug. Res Vet Sci 86:438–442. https://doi.org/10.1016/j.rvsc.2008.10.002
doi: 10.1016/j.rvsc.2008.10.002
pubmed: 19014875
Greer KA, Wong AK, Liu H, Famula TR, Pedersen NC, Ruhe A et al (2010) Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis. Tissue Antigens 76:110–118. https://doi.org/10.1111/j.1399-0039.2010.01484.x
doi: 10.1111/j.1399-0039.2010.01484.x
pubmed: 20403140
Hainfellner JA, Voigtlander T, Strobel T, Mazal PR, Maddalena AS, Aguzzi A et al (2001) Fibroblasts can express glial fibrillary acidic protein (GFAP) in vivo. J Neuropathol Exp Neurol 60:449–461. https://doi.org/10.1093/jnen/60.5.449
doi: 10.1093/jnen/60.5.449
pubmed: 11379820
Iorio R, Damato V, Evoli A, Gessi M, Gaudino S, Di Lazzaro V et al (2018) Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. J Neurol Neurosurg Psychiatry 89:138–146. https://doi.org/10.1136/jnnp-2017-316583
doi: 10.1136/jnnp-2017-316583
pubmed: 28951498
Kim SY, Li J, Bentsman G, Brooks AI, Volsky DJ (2004) Microarray analysis of changes in cellular gene expression induced by productive infection of primary human astrocytes: implications for HAD. J Neuroimmunol 157:17–26. https://doi.org/10.1016/j.jneuroim.2004.08.032
doi: 10.1016/j.jneuroim.2004.08.032
pubmed: 15579276
Kimura A, Kato S, Takekoshi A, Yoshikura N, Yanagida N, Kitaguchi H et al (2021) Autoimmune glial fibrillary acidic protein astrocytopathy resembling isolated central nervous system lymphomatoid granulomatosis. J Neuroimmunol 361:577748. https://doi.org/10.1016/j.jneuroim.2021.577748
doi: 10.1016/j.jneuroim.2021.577748
pubmed: 34653948
Kimura A, Takekoshi A, Yoshikura N, Hayashi Y, Shimohata T (2019) Clinical characteristics of autoimmune GFAP astrocytopathy. J Neuroimmunol 332:91–98. https://doi.org/10.1016/j.jneuroim.2019.04.004
doi: 10.1016/j.jneuroim.2019.04.004
pubmed: 30991306
Kong W, Montano M, Corley MJ, Helmy E, Kobayashi H, Kinisu M et al (2022) Neuropilin-1 mediates SARS-CoV-2 infection of astrocytes in brain organoids, inducing inflammation leading to dysfunction and death of neurons. MBio 13:e0230822
doi: 10.1128/mbio.02308-22
pubmed: 36314791
Kunchok A, Zekeridou A, McKeon A (2019) Autoimmune glial fibrillary acidic protein astrocytopathy. Curr Opin Neurol 32:452–458. https://doi.org/10.1097/WCO.0000000000000676
doi: 10.1097/WCO.0000000000000676
pubmed: 30724768
pmcid: 6522205
Long Y, Liang J, Xu H, Huang Q, Yang J, Gao C et al (2018) Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur J Neurol 25:477–483. https://doi.org/10.1111/ene.13531
doi: 10.1111/ene.13531
pubmed: 29193473
Martin AL, Jolliffe E, Hertweck SP (2018) Ovarian teratoma associated with coexisting anti-N-methyl-D-aspartate receptor and glial fibrillary acidic protein autoimmune meningoencephalitis in an adolescent girl: a case report. J Pediatr Adolesc Gynecol 31:321–324. https://doi.org/10.1016/j.jpag.2017.12.009
doi: 10.1016/j.jpag.2017.12.009
pubmed: 29294378
Martinez-Hernandez E, Guasp M, Garcia-Serra A, Maudes E, Arino H, Sepulveda M et al (2020) Clinical significance of anti-NMDAR concurrent with glial or neuronal surface antibodies. Neurology 94:e2302–e2310. https://doi.org/10.1212/WNL.0000000000009239
doi: 10.1212/WNL.0000000000009239
pubmed: 32161029
Matsuki N, Takahashi M, Yaegashi M, Tamahara S, Ono K (2009) Serial examinations of anti-GFAP autoantibodies in cerebrospinal fluids in canine necrotizing meningoencephalitis. J Vet Med Sci 71:99–100. https://doi.org/10.1292/jvms.71.99
doi: 10.1292/jvms.71.99
pubmed: 19194083
McNally AK, Anderson JM (1995) Interleukin-4 induces foreign body giant cells from human monocytes/macrophages. Differential lymphokine regulation of macrophage fusion leads to morphological variants of multinucleated giant cells. Am J Pathol 147:1487–1499
pubmed: 7485411
pmcid: 1869534
Michailidou I, Naessens DM, Hametner S, Guldenaar W, Kooi EJ, Geurts JJ et al (2017) Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: Implication for disease pathogenesis. Glia 65:264–277. https://doi.org/10.1002/glia.23090
doi: 10.1002/glia.23090
pubmed: 27778395
Michailidou I, Willems JG, Kooi EJ, van Eden C, Gold SM, Geurts JJ et al (2015) Complement C1q–C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol 77:1007–1026. https://doi.org/10.1002/ana.24398
doi: 10.1002/ana.24398
pubmed: 25727254
Miyake H, Inoue A, Tanaka M, Matsuki N (2013) Serum glial fibrillary acidic protein as a specific marker for necrotizing meningoencephalitis in Pug dogs. J Vet Med Sci 75:1543–1545. https://doi.org/10.1292/jvms.13-0252
doi: 10.1292/jvms.13-0252
pubmed: 23856761
pmcid: 3942992
Paul P, McKeon A, Pittock SJ, Klein CJ, Shah S, Toledano M et al (2020) GFAP IgG associated inflammatory polyneuropathy. J Neuroimmunol 343:577233. https://doi.org/10.1016/j.jneuroim.2020.577233
doi: 10.1016/j.jneuroim.2020.577233
pubmed: 32272393
Pedersen N, Liu H, Millon L, Greer K (2011) Dog leukocyte antigen class II-associated genetic risk testing for immune disorders of dogs: simplified approaches using Pug dog necrotizing meningoencephalitis as a model. J Vet Diagn Invest 23:68–76. https://doi.org/10.1177/104063871102300110
doi: 10.1177/104063871102300110
pubmed: 21217030
Quek AM, Tang D, Chin A, Ng KW, Lin H, Seet RC (2022) Autoimmune glial fibrillary acidic protein astrocytopathy masquerading as tuberculosis of the central nervous system: a case series. Int J Infect Dis 124:164–167. https://doi.org/10.1016/j.ijid.2022.09.029
doi: 10.1016/j.ijid.2022.09.029
pubmed: 36162739
Rapino F, Natoli T, Limone F, O’Connor E, Blank J, Tegtmeyer M et al (2023) Small-molecule screen reveals pathways that regulate C4 secretion in stem cell-derived astrocytes. Stem Cell Rep 18:237–253. https://doi.org/10.1016/j.stemcr.2022.11.018
doi: 10.1016/j.stemcr.2022.11.018
Safra N, Pedersen NC, Wolf Z, Johnson EG, Liu HW, Hughes AM et al (2011) Expanded dog leukocyte antigen (DLA) single nucleotide polymorphism (SNP) genotyping reveals spurious class II associations. Vet J 189:220–226. https://doi.org/10.1016/j.tvjl.2011.06.023
doi: 10.1016/j.tvjl.2011.06.023
pubmed: 21741283
pmcid: 3152640
Sasaki K, Bean A, Shah S, Schutten E, Huseby PG, Peters B et al (2014) Relapsing-remitting central nervous system autoimmunity mediated by GFAP-specific CD8 T cells. J Immunol 192:3029–3042. https://doi.org/10.4049/jimmunol.1302911
doi: 10.4049/jimmunol.1302911
pubmed: 24591371
Schrauwen I, Barber RM, Schatzberg SJ, Siniard AL, Corneveaux JJ, Porter BF et al (2014) Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds. PLoS ONE 9:e112755. https://doi.org/10.1371/journal.pone.0112755
doi: 10.1371/journal.pone.0112755
pubmed: 25393235
pmcid: 4231098
Shibuya M, Matsuki N, Fujiwara K, Imajoh-Ohmi S, Fukuda H, Pham NT et al (2007) Autoantibodies against glial fibrillary acidic protein (GFAP) in cerebrospinal fluids from Pug dogs with necrotizing meningoencephalitis. J Vet Med Sci 69:241–245. https://doi.org/10.1292/jvms.69.241
doi: 10.1292/jvms.69.241
pubmed: 17409638
Shu Y, Long Y, Chang Y, Li R, Sun X, Wang Y et al (2018) Brain immunohistopathology in a patient with autoimmune glial fibrillary acidic protein astrocytopathy. NeuroImmunoModulation 25:1–6. https://doi.org/10.1159/000488879
doi: 10.1159/000488879
pubmed: 29788018
Stam NJ, Vroom TM, Peters PJ, Pastoors EB, Ploegh HL (1990) HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol 2:113–125. https://doi.org/10.1093/intimm/2.2.113
doi: 10.1093/intimm/2.2.113
pubmed: 2088481
Theuriet J, Cluse F, Gravier-Dumonceau A, Picard G, Closs S, Rogemond V et al (2023) Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease. J Neurol 270:5545–5560. https://doi.org/10.1007/s00415-023-11908-7
doi: 10.1007/s00415-023-11908-7
pubmed: 37540278
pmcid: 10576672
Toda Y, Matsuki N, Shibuya M, Fujioka I, Tamahara S, Ono K (2007) Glial fibrillary acidic protein (GFAP) and anti-GFAP autoantibody in canine necrotising meningoencephalitis. Vet Rec 161:261–264. https://doi.org/10.1136/vr.161.8.261
doi: 10.1136/vr.161.8.261
pubmed: 17720962
Uchida K, Hasegawa T, Ikeda M, Yamaguchi R, Tateyama S (1999) Detection of an autoantibody from Pug dogs with necrotizing encephalitis (Pug dog encephalitis). Vet Pathol 36:301–307. https://doi.org/10.1354/vp.36-4-301
doi: 10.1354/vp.36-4-301
pubmed: 10421096
Walker DG, Kim SU, McGeer PL (1998) Expression of complement C4 and C9 genes by human astrocytes. Brain Res 809:31–38. https://doi.org/10.1016/s0006-8993(98)00811-7
doi: 10.1016/s0006-8993(98)00811-7
pubmed: 9795119
Wickel J, Chung HY, Kirchhof K, Boeckler D, Merkelbach S, Kuzman P et al (2020) Encephalitis with radial perivascular emphasis: Not necessarily associated with GFAP antibodies. Neurol Neuroimmunol Neuroinflamm. https://doi.org/10.1212/NXI.0000000000000670
doi: 10.1212/NXI.0000000000000670
pubmed: 32019875
pmcid: 7051210
Williams JP, Carlson NG, Greenlee JE (2018) Antibodies in autoimmune human neurological disease: pathogenesis and immunopathology. Semin Neurol 38:267–277. https://doi.org/10.1055/s-0038-1660501
doi: 10.1055/s-0038-1660501
pubmed: 30011408
Xiao J, Chen X, Shang K, Tang Y, Chen M, Deng G et al (2021) Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study. J Neuroimmunol 360:577718. https://doi.org/10.1016/j.jneuroim.2021.577718
doi: 10.1016/j.jneuroim.2021.577718
pubmed: 34600199
Yamakawa M, Hogan KO, Leever J, Jassam YN (2021) Autopsy case of meningoencephalomyelitis associated with glial fibrillary acidic protein antibody. Neurol Neuroimmunol Neuroinflamm. https://doi.org/10.1212/NXI.0000000000001081
doi: 10.1212/NXI.0000000000001081
pubmed: 34642236
pmcid: 8515200
Yang X, Liang J, Huang Q, Xu H, Gao C, Long Y et al (2017) Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. NeuroImmunoModulation 24:113–119. https://doi.org/10.1159/000479948
doi: 10.1159/000479948
pubmed: 28922662
Yang X, Xu H, Ding M, Huang Q, Chen B, Yang H et al (2018) Overlapping autoimmune syndromes in patients with glial fibrillary acidic protein antibodies. Front Neurol 9:251. https://doi.org/10.3389/fneur.2018.00251
doi: 10.3389/fneur.2018.00251
pubmed: 29755396
pmcid: 5932346
Yasojima K, Schwab C, McGeer EG, McGeer PL (1999) Up-regulated production and activation of the complement system in Alzheimer’s disease brain. Am J Pathol 154:927–936. https://doi.org/10.1016/S0002-9440(10)65340-0
doi: 10.1016/S0002-9440(10)65340-0
pubmed: 10079271
pmcid: 1866427
Yuan Z, Li H, Huang L, Fu C, Chen Y, Zhi C et al (2021) CD8(+) T-cell predominance in autoimmune glial fibrillary acidic protein astrocytopathy. Eur J Neurol 28:2121–2125. https://doi.org/10.1111/ene.14778
doi: 10.1111/ene.14778
pubmed: 33590610