Anti-IgLON5 disease: relationship between neuroimmunology and neurodegeneration

Abstract

Abstract:

Anti-IgLON5 disease is a rare autoimmune encephalitis (AE) with anti-IgLON5 antibodies in serum and/or CSF, which was first reported in 2014. Different from the traditional AE, anti-IgLON5 disease presents dual characteristics of neuroimmunity and neurodegeneration. Autopsy of some patients showed phosphorylated tau deposition, mainly in hypothalamus and brainstem tegmentum. The discovery of anti-IgLON5 disease reveals a potential crosslink between neuroimmunology and neurodegeneration, and may become a breakthrough in studying the interplay between the two mechanisms, which means that the immune inflammation induces the deposition of phosphorylated tau protein. Neuroimmunity may participate in and promote the occurrence and development of neurodegeneration. Neuroimmunity may be the trigger of neurodegeneration.

Key words:Anti-IgLON5 disease,Encephalitis,Autoimmune disease,Neurodegeneration

CLC Number:

R715.2

CHEN Sheng, ZHANG Yizongheng. Anti-IgLON5 disease: relationship between neuroimmunology and neurodegeneration[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(06): 663-668.

References29

[1]	Sabater L, Gaig C, Gelpi E, et al. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study[J]. Lancet Neurol, 2014, 13(6):575-586. doi:10.1016/S1474-4422(14)70051-1pmid:24703753
[2]	Grüter T, Möllers F E, Tietz A, et al. Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease[J]. Brain, 2023, 146(2):600-611. doi:10.1093/brain/awac090 URL
[3]	Vanaveski T, Singh K, Narvik J, et al. Promoter-Specific Expression and Genomic Structure of IgLON Family Genes in Mouse[J]. Front Neurosci, 2017, 11:38.
[4]	Zhang Y H, Ni Y, Gao Y N, et al. Anti-IgLON5 disease: a novel topic beyond neuroimmunology[J]. Neural Regen Res, 2023, 18(5):1017-1022. doi:10.4103/1673-5374.355742 URL
[5]	Lim J H, Beg M M A, Ahmad K, et al. IgLON5 Regulates the Adhesion and Differentiation of Myoblasts[J]. Cells, 2021, 10(2):417. doi:10.3390/cells10020417 URL
[6]	Karis K, Eskla K L, Kaare M, et al. Altered Expression Profile of IgLON Family of Neural Cell Adhesion Molecules in the Dorsolateral Prefrontal Cortex of Schizophrenic Patients[J]. Front Mol Neurosci, 2018, 11:8. doi:10.3389/fnmol.2018.00008pmid:29434535
[7]	Chen W, Huang J, Xiong J, et al. Identification of a Tumor Microenvironment-Related Gene Signature Indicative of Disease Prognosis and Treatment Response in Colon Cancer[J]. Oxid Med Cell Longev, 2021, 2021:6290261.
[8]	Xiong W, Feng S, Wang H, et al. Identification of candidate genes and pathways in limonin-mediated cardiac repair after myocardial infarction[J]. Biomed Pharmacother, 2021, 142:112088. doi:10.1016/j.biopha.2021.112088pmid:34470729
[9]	Gaig C, Ercilla G, Daura X, et al. HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease[J]. Neurol Neuroimmunol Neuroinflamm, 2019, 6(6):e605. doi:10.1212/NXI.0000000000000605 URL
[10]	Strippel C, Heidbreder A, Schulte-Mecklenbeck A, et al. Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease: A Case Series[J]. Neurol Neuroimmunol Neuroinflamm, 2022, 9(2):e1137.
[11]	Sabater L, Planagumà J, Dalmau J, et al. Cellular investigations with human antibodies associated with the anti-IgLON5 syndrome[J]. J Neuroinflammation, 2016, 13(1):226. doi:10.1186/s12974-016-0689-1 URL
[12]	Landa J, Gaig C, Plagumà J, et al. Effects of IgLON5 Antibodies on Neuronal Cytoskeleton: A Link between Autoimmunity and Neurodegeneration[J]. Ann Neurol, 2020, 88(5):1023-1027. doi:10.1002/ana.v88.5 URL
[13]	Ryding M, Gamre M, Nissen M S, et al. Neurodegeneration Induced by Anti-IgLON5 Antibodies Studied in Induced Pluripotent Stem Cell-Derived Human Neurons[J]. Cells, 2021, 10(4):837. doi:10.3390/cells10040837 URL
[14]	Alvente S, Matteoli G, Molina-Porcel L, et al. Pilot Study of the Effects of Chronic Intracerebroventricular Infusion of Human Anti-IgLON5 Disease Antibodies in Mice[J]. Cells, 2022, 11(6):1024. doi:10.3390/cells11061024 URL
[15]	Ni Y, Feng Y, Shen D, et al. Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice[J]. J Neuroinflammation, 2022, 19(1):140. doi:10.1186/s12974-022-02520-z
[16]	Ye F, Fan C, Peng M, et al. Anti-IgLON5 disease in a pediatric patient with Langerhans cell histiocytosis[J]. Clin Chim Acta, 2021, 521:212-214. doi:10.1016/j.cca.2021.07.008pmid:34270954
[17]	Gelpi E, Höftberger R, Graus F, et al. Neuropathological criteria of anti-IgLON5-related tauopathy[J]. Acta Neuropathol, 2016, 132(4):531-543. doi:10.1007/s00401-016-1591-8pmid:27358064
[18]	Schöberl F, Levin J, Remi J, et al. IgLON5: A case with predominant cerebellar tau deposits and leptomeningeal inflammation[J]. Neurology, 2018, 91(4):180-182. doi:10.1212/WNL.0000000000005859pmid:29970401
[19]	Erro M E, Sabater L, Martínez L, et al. Anti-IGLON5 disease: A new case without neuropathologic evidence of brainstem tauopathy[J]. Neurol Neuroimmunol Neuroinflamm, 2019, 7(2):e651. doi:10.1212/NXI.0000000000000651 URL
[20]	Montagna M, Amir R, De Volder I, et al. IgLON5-Associated Encephalitis With Atypical Brain Magnetic Resonance Imaging and Cerebrospinal Fluid Changes[J]. Front Neurol, 2018, 9:329. doi:10.3389/fneur.2018.00329pmid:29867738
[21]	Cabezudo-García P, Mena-Vázquez N, Estivill Torrús G, et al. Response to immunotherapy in anti-IgLON5 disease: A systematic review[J]. Acta Neurol Scand, 2020, 141(4):263-270. doi:10.1111/ane.13207pmid:31853949
[22]	Hughes E G, Peng X, Gleichman A J, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis[J]. J Neurosci, 2010, 30(17):5866-5875. doi:10.1523/JNEUROSCI.0167-10.2010pmid:20427647
[23]	Scheggia D, Stanic J, Italia M, et al. GluA3 autoantibo-dies induce alterations in dendritic spine and behavior in mice[J]. Brain Behav Immun, 2021, 97:89-101. doi:10.1016/j.bbi.2021.07.001pmid:34246733
[24]	Alberti P, Semperboni S, Cavaletti G, et al. Neurons: The Interplay between Cytoskeleton, Ion Channels/Transporters and Mitochondria[J]. Cells, 2022, 11(16):2499. doi:10.3390/cells11162499 URL
[25]	Dendrou C A, Fugger L, Friese M A. Immunopathology of multiple sclerosis[J]. Nat Rev Immunol, 2015, 15(9):545-558. doi:10.1038/nri3871pmid:26250739
[26]	Howell O W, Reeves C A, Nicholas R, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis[J]. Brain, 2011, 134(Pt 9):2755-2771. doi:10.1093/brain/awr182pmid:21840891
[27]	Correale J, Gaitán M I, Ysrraelit M C, et al. Progressive multiple sclerosis: from pathogenic mechanisms to treatment[J]. Brain, 2017, 140(3):527-546. doi:10.1093/brain/aww258pmid:27794524
[28]	Meier-Stephenson F S, Meier-Stephenson V C, Carter M D, et al. Alzheimer′s disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites[J]. Alzheimers Dement (N Y), 2022, 8(1):e12283.
[29]	Tan E K, Chao Y X, West A, et al. Parkinson disease and the immune system-associations, mechanisms and therapeutics[J]. Nat Rev Neurol, 2020, 16(6):303-318. doi:10.1038/s41582-020-0344-4