Anti-IgLON5 disease

Last updated
Anti-IgLON5 disease
Specialty Immunology

Anti-IgLON5 disease is an uncommon neurological autoimmune condition linked to autoantibodies directed against the IgLON5 protein. [1] Sleep disturbance, bulbar symptoms, and abnormal gait make up the majority of the clinical presentation, which is then followed by cognitive dysfunction. [2] The diagnosis of anti-IgLON5 disease is primarily based on clinical signs and the identification of IgLON5 antibodies in patient serum and/or cerebrospinal fluid. [1]

Contents

Mechanism

The IgLON proteins are a family of five cell-adhesion molecules IgLON 1, 2, 3, 4 & 5, which assist in neuronal growth and connections among nerve cells. [3] and help in brain evolution and maturation to maintain integrity of the blood brain barrier. [4]

Abnormal pTau deposits seen in several brains, brain stems and upper cervical cords shown by neuro-immuno-histochemistry studies of brain tissue from these regions without inflammatory cells differentiate this entity from other autoimmune encephalitis. [5] [6]

IgLON5 refers to a cell surface protein involved in promoting connections among nerve cells. [7] Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease. [8] The sleep problems seen in this disorder are insomnia, sleep related abnormal movements called parasomnias which may be seen in both REM and NREM sleep and poor efficiency of sleep. Respiratory problems related to sleep disorder such as obstructive sleep apnea (OSA) and jerky stertorous breathing were noted in more than half the cases. [9]

Diagnosis

Serum studies show IgLON5 antibodies in almost all patients while the presence of CSF antibodies is more sporadic, occurring in ~50% of cases. Additional findings may be Oligoclonal bands(OCB), a few leukocytes and a slight rise in proteins, with otherwise normal CSF examination in more than half the cases. [10]

Genetics and Hereditary Risk

Anti-IgLON5 disease is not considered a hereditary disorder. Instead, it is classified as an autoimmune disease in which the immune system produces antibodies against the neuronal cell adhesion molecule IgLON5.

Studies have shown a strong association with specific human leukocyte antigen (HLA) types, particularly HLA-DRB1*10:01 and HLA-DQB1*05:01 alleles, suggesting a role for genetic susceptibility in disease development. [11] [12]

However, these HLA alleles are not disease-causing on their own, and the presence of such genetic markers in family members does not predict disease occurrence. To date, no familial clustering or inherited cases have been reported. As such, routine genetic or antibody testing of relatives is not recommended unless symptoms develop.

Treatment

Anti-IgLON5 disease is mainly treated with immunosuppressants (80%), mostly cycles of IV corticosteroids (58%) in combination with IV immunoglobulins (IVIg−36%) and/or TPE (27%). Alternative successfully used, second-line treatments are Rituximab (22%) and Cyclophosphamide (12%), Azathioprine and Mycophenolate Mofetil. [13] [14] [15]

Sudden death is the most common outcome in nearly 34% of patients, irrespective of partial response to therapy. While complications from aspiration were the other common cause of death. [16] [17] [18]

Symptomatic treatment with CPAP in patients with OSA helps improve respiratory symptoms, while parasomnias and movement disorders (myoclonus, parkinsonism, and dystonia) did not respond when antiepileptic, dopaminergic, and anti-hyperkinetic drugs were administered. [13] [18] [19]

References

  1. 1 2 Zhou, Qin-Ming; Hu, Ji; Chen, Sheng; Zhang, Yi-ZongHeng; Ni, You; Gao, Yi-Ning; Shen, Ding-Ding; He, Lu; Yin, Dou; Meng, Huan-Yu (2023). "Anti-IgLON5 disease: a novel topic beyond neuroimmunology". Neural Regeneration Research. 18 (5). Medknow: 1017–1022. doi: 10.4103/1673-5374.355742 . ISSN   1673-5374. PMC   9827781 . PMID   36254983.
  2. ↑ Madetko, Natalia; Marzec, Weronika; Kowalska, Agata; Przewodowska, Dominika; Alster, Piotr; Koziorowski, Dariusz (March 1, 2022). "Anti-IgLON5 Disease – The Current State of Knowledge and Further Perspectives". Frontiers in Immunology. 13 852215. Frontiers Media SA. doi: 10.3389/fimmu.2022.852215 . ISSN   1664-3224. PMC   8921982 . PMID   35300333.
  3. ↑ Ranaivoson FM, Turk LS, Ozgul S, Kakehi S, von Daake S, Lopez N, et al. (June 2019). "A Proteomic Screen of Neuronal Cell-Surface Molecules Reveals IgLONs as Structurally Conserved Interaction Modules at the Synapse". Structure. 27 (6): 893–906.e9. doi:10.1016/j.str.2019.03.004. PMC   6609445 . PMID   30956130.
  4. ↑ Kubick N, Brösamle D, Mickael ME (January 2018). "Molecular Evolution and Functional Divergence of the IgLON Family". Evolutionary Bioinformatics Online. 14 1176934318775081. doi:10.1177/1176934318775081. PMC   5967153 . PMID   29844654.
  5. ↑ Gelpi E, Höftberger R, Graus F, Ling H, Holton JL, Dawson T, et al. (October 2016). "Neuropathological criteria of anti-IgLON5-related tauopathy". Acta Neuropathologica. 132 (4): 531–43. doi:10.1007/s00401-016-1591-8. PMC   5023728 . PMID   27358064.
  6. ↑ Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc (2014). "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". The Lancet Neurology. 13 (6). Elsevier BV: 575–586. doi:10.1016/s1474-4422(14)70051-1. ISSN   1474-4422. PMC   4104022 . PMID   24703753.
  7. ↑ Database, GeneCards Human Gene. "IGLON5 Gene - GeneCards | IGLO5 Protein | IGLO5 Antibody". www.genecards.org. Retrieved 16 June 2018.
  8. ↑ Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, et al. (May 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC   5409845 . PMID   28381508.
  9. ↑ Nissen, Mette Scheller; Blaabjerg, Morten (2019). "Anti-IgLON5 Disease: A Case With 11-Year Clinical Course and Review of the Literature". Frontiers in Neurology. 10 1056. doi: 10.3389/fneur.2019.01056 . PMC   6783555 . PMID   31632341.
  10. ↑ Solnes, Lilja B (2017). "Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis". Journal of Nuclear Medicine. 58 (8): 1307–1313. doi:10.2967/jnumed.116.184333. PMC   6944181 . PMID   28209905.
  11. ↑ Pierro, S. (2024). "Further insights into anti-IgLON5 disease: a case with complex clinical presentation". BMC Neurology. 24 (1) 334: 322. doi: 10.1186/s12883-024-03837-3 . PMID   39256712.
  12. ↑ Inga, K. (2024). "HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease". Frontiers in Immunology. 15 1376456. doi: 10.3389/fimmu.2024.1376456 . PMID   38827736.
  13. 1 2 Haitao R, Yingmai Y, Yan H, Fei H, Xia L, Honglin H, et al. (November 2016). "Chorea and parkinsonism associated with autoantibodies to IgLON5 and responsive to immunotherapy". Journal of Neuroimmunology. 300: 9–10. doi:10.1016/j.jneuroim.2016.09.012. PMID   27806876. S2CID   206278688.
  14. ↑ Montagna M, Amir R, De Volder I, Lammens M, Huyskens J, Willekens B (2018-05-17). "IgLON5-Associated Encephalitis With Atypical Brain Magnetic Resonance Imaging and Cerebrospinal Fluid Changes". Frontiers in Neurology. 9 329. doi: 10.3389/fneur.2018.00329 . PMC   5966542 . PMID   29867738.
  15. ↑ Schöberl F, Levin J, Remi J, Goldschagg N, Eren O, Okamura N, et al. (July 2018). "IgLON5: A case with predominant cerebellar tau deposits and leptomeningeal inflammation". Neurology. 91 (4): 180–182. doi:10.1212/WNL.0000000000005859. PMID   29970401. S2CID   49680135.
  16. ↑ Schröder JB, Melzer N, Ruck T, Heidbreder A, Kleffner I, Dittrich R, et al. (January 2017). "Isolated dysphagia as initial sign of anti-IgLON5 syndrome". Neurology. 4 (1) e302. doi:10.1212/NXI.0000000000000302. PMC   5120591 . PMID   27900347.
  17. ↑ Wenninger S (2017-11-21). "Expanding the Clinical Spectrum of IgLON5-Syndrome". Journal of Neuromuscular Diseases. 4 (4): 337–339. doi:10.3233/JND-170259. PMID   29103046.
  18. 1 2 Bahtz R, Teegen B, Borowski K, Probst C, Blöcker IM, Fechner K, et al. (October 2014). "Autoantibodies against IgLON5: Two new cases". Journal of Neuroimmunology. 275 (1–2): 8. doi:10.1016/j.jneuroim.2014.08.027. S2CID   53172498.
  19. ↑ Brüggemann N, Wandinger KP, Gaig C, Sprenger A, Junghanns K, Helmchen C, Münchau A (May 2016). "Dystonia, lower limb stiffness, and upward gaze palsy in a patient with IgLON5 antibodies". Movement Disorders. 31 (5): 762–4. doi:10.1002/mds.26608. PMID   27030137. S2CID   3443301.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.