Serum antiganglioside antibodies in patients with autoimmune limbic encephalitis

Serum antiganglioside antibodies in patients with autoimmune limbic encephalitis

Background/aim: Ganglioside antibodies are identified not only in patients with inflammatory neuropathies but also several central nervous system disorders and paraneoplastic neuropathies. Our aim was to investigate whether ganglioside antibodies are found in autoimmune encephalitis patients and may function as a diagnostic and prognostic biomarker. Materials and methods: Sera and cerebrospinal fluid (CSF) samples of 33 patients fulfilling the criteria for probable autoimmune encephalitis were collected within the first week of clinical manifestation. None of the patients had evident symptoms and findings of peripheral polyneuropathy. Well-characterized antineuronal and paraneoplastic antibodies were investigated in sera and CSF and antiganglioside (antiGM1, GM2, GM3, GD1a, GD1b, GT1b, and GQ1b) IgG and IgM antibodies were measured in sera using commercial immunoblots. Results: Twenty-eight of 33 autoimmune encephalitis patients displayed antibodies against neuronal surface or onco-neural antigens with N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase (GAD) and Hu antibodies being the most prevalent. While no antiganglioside IgG antibodies were found, 4 patients (2 anti-NMDAR+, 1 anti-GAD+ and 1 antibody negative) with autoimmune limbic encephalitis displayed anti-GM1, anti-GM2, anti-GM3 or anti-GQ1b IgM antibodies. There was no apparent association between antiganglioside positivity and clinical and demographic features. Conclusion: Serum ganglioside IgM antibodies may infrequently emerge during the clinical course of autoimmune limbic encephalitis without evident polyneuropathy. Absence of the IgG response suggests that these antibodies might have developed as a hyperacute immune response to neuro-axonal destruction. Nevertheless, potential impact of ganglioside antibodies on axonal degeneration and neuronal loss in limbic encephalitis pends to be further investigated.Key words: Ganglioside, antibody, autoimmune encephalitis, paraneoplastic, autoimmunity

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  • 1. Wanleenuwat P, Iwanowski P, Kozubski W. Antiganglioside antibodies in neurological diseases. Journal of the Neurological Sciences 2020; 408: 116576. doi: 10.1016/j.jns.2019.116576
  • 2. Colsch B, Jackson SN, Dutta S, Woods AS. Molecular microscopy of brain gangliosides: illustrating their distribution in hippocampal cell layers. ACS Chemical Neuroscience 2011; 2 (4): 213-222. doi: 10.1021/cn100096h
  • 3. Timarova G, Lisa I, Kukumberg P. Long-term effect of rituximab in a case with late-onset Rasmussen´s encephalitis with anti-ganglioside IgGQ1b and anti-GAD antibodies positivity. Case Report. Neuro Endocrinology Letters 2016; 37 (3): 179-183.
  • 4. Çoban A, Ulusoy C, Giriş M, Turan S, Türkoğlu R et al. Serum anti-neuronal antibodies in amyotrophic lateral sclerosis. The International Journal of Neuroscience 2013; 123 (8): 557-562.
  • 5. Ding Y, Yu L, Zhou S, Zhang L. Clinical characteristic analysis of seven children with bickerstaff brainstem encephalitis in China. Frontiers in Neurology 2020; 11: 557. doi: 10.3389/ fneur.2020.00557
  • 6. Merwick A, Dalmau J, Delanty N. Insights into antibodyassociated encephalitis Bickerstaff ’s 1950’s papers revisited. Journal of the Neurological Sciences 2013; 334 (1-2): 167-168. doi: 10.1016/j.jns.2013.07.010
  • 7. Kornberg AJ, Pestronk A, Blume GM, Lopate G, Yue J et al. Selective staining of the cerebellar molecular layer by serum IgG in Miller-Fisher and related syndromes. Neurology 1996; 47 (5): 1317-1320. doi: 10.1212/wnl.47.5.1317
  • 8. Tüzün E, Kürtüncü M, Lang B, Içöz S, Akman-Demir G et al. Bickerstaff ’s encephalitis and Miller Fisher syndrome associated with voltage-gated potassium channel and novel anti-neuronal antibodies. European Journal of Neurology 2010; 17 (10): 1304-1307. doi: 10.1111/j.1468-1331.2010.02993.x
  • 9. De Toni L, Marconi S, Nardelli E, Alberti D, Borsellino G et al. Gangliosides act as onconeural antigens in paraneoplastic neuropathies. Journal of Neuroimmunology 2004; 156 (1-2): 178-187. doi: 10.1016/j.jneuroim.2004.07.020
  • 10. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG et al. A clinical approach to diagnosis of autoimmune encephalitis. The Lancet Neurology 2016; 15 (4): 391-404. doi: 10.1016/S1474- 4422(15)00401-9
  • 11. Gallagher S, Winston SE, Fuller SA, Hurrell JG. Immunoblotting and immunodetection. Current Protocols in Cell Biology 2011; 6 (6.2). doi: 10.1002/0471143030.cb0602s52
  • 12. Cutillo G, Saariaho AH, Meri S. Physiology of gangliosides and the role of antiganglioside antibodies in human diseases. Cellular & Molecular Immunology 2020; 17 (4): 313-322. doi: 10.1038/s41423-020-0388-9
  • 13. Blackburn KM, Wang C. Post-infectious neurological disorders. Therapeutic Advances in Neurological Disorders 2020; 13.. doi: 10.1177/1756286420952901
  • 14. Shitara K, Fujiwara K, Igarashi S, Ohta S, Furuya A et al. Immunoglobulin class switch of anti-ganglioside monoclonal antibody from IgM to IgG. Journal of Immunological Methods 1994; 169 (1): 83-92. doi: 10.1016/0022-1759(94)90127-9
  • 15. Miyakawa H, Kikuchi K, Kitazawa E, Kawaguchi N. Anti-pyruvate dehydrogenase complex-E2 antibody immunoglobulin class switch from IgM to IgG in long-term follow-up patients with primary biliary cirrhosis. Hepatology Research 2002; 22 (3): 167-173. doi: 10.1016/s1386- 6346(01)00129-2
  • 16. Hara M, Martinez-Hernandez E, Ariño H, Armangué T, Spatola M et al. Clinical and pathogenic significance of IgG, IgA, and IgM antibodies against the NMDA receptor. Neurology 2018; 90 (16): e1386-e1394.
  • 17. Abbas A, Lichtman A, Pillai Shiv. Chapter 12. B Cell Activation and Antibody Production. Cellular and Molecular Immunology. 9th ed. Philadelphia, PA, USA: Elsevier; 2018. pp. 251-273
  • 18. Chapman PB, Morrissey DM, Panageas KS, Hamilton WB, Zhan C et al. Induction of antibodies against GM2 ganglioside by immunizing melanoma patients using GM2-keyhole limpet hemocyanin + QS21 vaccine: a dose-response study. Clinical Cancer Research 2000; 6 (3): 874-879.
  • 19. Shin MK, Jung WR, Kim HG, Roh SE, Kwak CH et al. The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway. Neuropharmacology 2014; 77: 414-421. doi: 10.1016/j.neuropharm.2013.10.022
  • 20. Jung WR, Kim HG, Shin MK, Park DI, Kim KL. The effect of ganglioside GQ1b on the NMDA receptor signaling pathway in H19-7 cells and rat hippocampus. Neuroscience 2010; 165 (1): 159-167. doi: 10.1016/j.neuroscience.2009.10.012
  • 21. Graus F, Escudero D, Oleaga L, Bruna J, Villarejo-Galende A et al. Syndrome and outcome of antibody-negative limbic encephalitis. European Journal of Neurology 2018; 25 (8): 1011-1016. doi: 10.1111/ene.13661
  • 22. Koike Y, Suwabe T, Konno T, Umeda Y, Oyake M et al. A case of progressive encephalomyelitis with rigidity and myoclonus associated with anti-GAD, anti-glycine receptor and anti-GM1 antibodies. Rinsho Shinkeigaku 2015; 55 (2): 111-114.
  • 23. Hatano T, Shimada Y, Kono A, Kubo S, Yokoyama K, et al. Atypical Miller Fisher syndrome associated with glutamate receptor antibodies. BMJ Case Reports 2011; bcr0820103228. doi: 10.1136/bcr.08.2010.3228
  • 24. Kaida K. Antibodies to glycoconjugates in autoimmune neuropathies. Clinical & Experimental Neuroimmunology 2015; 6: 387-394. doi: 10.1111/cen3.12267
  • 25. Zaro-Weber O, Galldiks N, Dohmen C, Fink GR, Nowak DA. Ocular flutter, generalized myoclonus, and trunk ataxia associated with anti-GQ1b antibodies. Archives of Neurology 2008; 65 (5): 659-661. doi: 10.1001/archneur.65.5.659
  • 26. Adams C, Diadori P, Schoenroth L, Fritzler M. Autoantibodies in childhood post-varicella acute cerebellar ataxia. The Canadian Journal of Neurological Sciences 2000; 27 (4): 316- 320. doi: 10.1017/s0317167100001074
  • 27. Tüzün E, Yaka E, Zuliani L, Içöz S, Baklan B et al. Steroidresponsive recurrent limbic encephalitis associated with small cell lung cancer and neuropil antibodies. Acta Neurologica Belgica 2011; 111 (2): 139-142.
  • 28. Yamada T, Bando H, Takeuchi S, Kita K, Li Q et al. Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by GM2-expressing smallcell lung cancer cells. Cancer Science 2011; 102 (12): 2157- 2163. doi: 10.1111/j.1349-7006.2011.02093.x
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
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