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大学・研究所にある論文を検索できる 「Circulating plasmablasts and follicular helper T-cell subsets are associated with antibody-positive autoimmune epilepsy」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Circulating plasmablasts and follicular helper T-cell subsets are associated with antibody-positive autoimmune epilepsy

Hara, Atsushi Chihara, Norio Akatani, Ritsu Nishigori, Ryusei Tsuji, Asato Yoshimura, Hajime Kawamoto, Michi Otsuka, Yoshihisa Kageyama, Yasufumi Kondo, Takayuki Leypoldt, Frank Wandinger, Klaus-Peter Matsumoto, Riki 神戸大学

2022.12.08

概要

Autoimmune epilepsy (AE) is an inflammatory disease of the central nervous system with symptoms that have seizures that are refractory to antiepileptic drugs. Since the diagnosis of AE tends to rely on a limited number of anti-neuronal antibody tests, a more comprehensive analysis of the immune background could achieve better diagnostic accuracy. This study aimed to compare the characteristics of anti-neuronal antibody-positive autoimmune epilepsy (AE/Ab(+)) and antibody-negative suspected autoimmune epilepsy (AE/Ab(-)) groups. A total of 23 patients who met the diagnostic criteria for autoimmune encephalitis with seizures and 11 healthy controls (HC) were enrolled. All patients were comprehensively analyzed for anti-neuronal antibodies; 13 patients were identified in the AE/Ab(+) group and 10 in the AE/Ab(-) group. Differences in clinical characteristics, including laboratory and imaging findings, were evaluated between the groups. In addition, the immunophenotype of peripheral blood mononuclear cells (PBMCs) and CSF mononuclear cells, particularly B cells and circulating Tfh (cTfh) subsets, and multiplex assays of serum and CSF were analyzed using flow cytometry. Patients with AE/Ab(+) did not show any differences in clinical parameters compared to patients with AE/Ab(-). However, the frequency of plasmablasts within PBMCs and CSF in patients with AE/Ab(+) was higher than that in patients with AE/Ab(-) and HC, and the frequency of cTfh17 cells and inducible T-cell co-stimulator (ICOS) expressing cTfh17 cells within cTfh subsets was higher than that in patients with AE/Ab(-). Furthermore, the frequency of ICOS(high)cTfh17 cells was positively correlated with that of the unswitched memory B cells. We also found that IL-12, IL-23, IL-6, IL-17A, and IFN-γ levels were elevated in the serum and IL-17A and IL-6 levels were elevated in the CSF of patients with AE/Ab(+). Our findings indicate that patients with AE/Ab(+) showed increased differentiation of B cells and cTfh subsets associated with antibody production. The elevated frequency of plasmablasts and ICOS expressing cTfh17 shift in PBMCs may be indicative of the presence of antibodies in patients with AE.

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参考文献

1. Ong MS, Kohane IS, Cai T, Gorman MP, Mandl KD. Population-level evidence for an autoimmune etiology of epilepsy. JAMA Neurol (2014) 71 (5):569–74. doi: 10.1001/jamaneurol.2014.188

2. Levite M. Autoimmune epilepsy. Nat Immunol (2002) 3(6):500. doi: 10.1038/ ni0602-500

3. Quek AM, Britton JW, McKeon A, So E, Lennon VA, Shin C, et al. Autoimmune epilepsy: Clinical characteristics and response to immunotherapy. Arch Neurol (2012) 69(5):582–93. doi: 10.1001/archneurol.2011.2985

4. Husari K, Dubey D. Autoimmune epilepsy. Neuroimmunology (2021), 189– 206. doi: 10.1007/978-3-030-61883-4_13

5. Dubey D, Kothapalli N, McKeon A, Flanagan EP, Lennon VA, Klein CJ, et al. Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction. J Neuroimmunol. (2018) 323:62–72. doi: 10.1016/j.jneuroim.2018.07.009

6. de Bruijn M, Bastiaansen AEM, Mojzisova H, van Sonderen A, Thijs RD, Majoie MJM, et al. Antibodies contributing to focal epilepsy signs and symptoms score. Ann Neurol (2021) 89(4):698–710. doi: 10.1002/ana.26013

7. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurology. (2016) 15 (4):391–404. doi: 10.1016/S1474-4422(15)00401-9

8. Ismail FS, Spatola M, Woermann FG, Popkirov S, Jungilligens J, Bien CG, et al. Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis. Eur J Neurol (2021) 1-8. doi: 10.1111/ene.15026

9. Graus F, Escudero D, Oleaga L, Bruna J, Villarejo-Galende A, Ballabriga J, et al. Syndrome and outcome of antibody-negative limbic encephalitis. Eur J Neurol (2018) 25(8):1011–6. doi: 10.1111/ene.13661

10. Jang Y, Kim DW, Yang KI, Byun JI, Seo JG, No YJ, et al. Clinical approach to autoimmune epilepsy. J Clin Neurol (2020) 16(4):519–29. doi: 10.3988/ jcn.2020.16.4.519

11. Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med (2018) 378(9):840–51. doi: 10.1056/NEJMra1708712

12. Schmitt N, Bentebibel SE, Ueno H. Phenotype and functions of memory tfh cells in human blood. Trends Immunol (2014) 35(9):436–42. doi: 10.1016/ j.it.2014.06.002

13. Ueno H, Banchereau J, Vinuesa CG. Pathophysiology of T follicular helper cells in humans and mice. Nat Immunol (2015) 16(2):142–52. doi: 10.1038/ni.3054

14. Brenna E, Davydov AN, Ladell K, McLaren JE, Bonaiuti P, Metsger M, et al. CD4(+) T follicular helper cells in human tonsils and blood are clonally convergent but divergent from non-tfh CD4(+) cells. Cell Rep (2020) 30(1):137–52 e5. doi: 10.1016/j.celrep.2019.12.016

15. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity (2011) 34(1):108–21. doi: 10.1016/j.immuni.2010.12.012

16. Ashida S, Ochi H, Hamatani M, Fujii C, Kimura K, Okada Y, et al. Immune skew of circulating follicular helper T cells associates with myasthenia gravis severity. Neurol Neuroimmunol Neuroinflamm (2021) 8(2):e945. doi: 10.1212/NXI.0000000000000945

17. Le Coz C, Joublin A, Pasquali JL, Korganow AS, Dumortier H, Monneaux F. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease. PloS One (2013) 8(9):e75319. doi: 10.1371/journal.pone.0075319

18. Bautista-Caro MB, Arroyo-Villa I, Castillo-Gallego C, de Miguel E, Peiteado D, Plasencia-Rodriguez C, et al. Decreased frequencies of circulating follicular helper T cell counterparts and plasmablasts in ankylosing spondylitis patients naive for TNF blockers. PloS One (2014) 9(9):e107086. doi: 10.1371/journal.pone.0107086

19. Kurata I, Matsumoto I, Sumida T. T Follicular helper cell subsets: a potential key player in autoimmunity. Immunol Med (2021) 44(1):1–9. doi: 10.1080/ 25785826.2020.1776079

20. Locci M, Havenar-Daughton C, Landais E, Wu J, Kroenke MA, Arlehamn CL, et al. Human circulating PD-1+CXCR3-CXCR5+ memory tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity (2013) 39(4):758–69. doi: 10.1016/j.immuni.2013.08.031

21. Li Y, Guptill JT, Russo MA, Howard JFJr., Massey JM, Juel VC, et al. Imbalance in T follicular helper cells producing IL-17 promotes pro-inflammatory responses in MuSK antibody positive myasthenia gravis. J Neuroimmunol. (2020) 345:577279. doi: 10.1016/j.jneuroim.2020.577279

22. Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. The generation of antibodysecreting plasma cells. Nat Rev Immunol (2015) 15(3):160–71. doi: 10.1038/nri3795

23. Olatunde AC, Hale JS, Lamb TJ. Cytokine-skewed tfh cells: functional consequences for b cell help. Trends Immunol (2021) 42(6):536–50. doi: 10.1016/ j.it.2021.04.006

24. Dalmau J. NMDA receptor encephalitis and other antibody-mediated disorders of the synapse. Neurology (2016) 87(23):2471–82. doi: 10.1212/ WNL.0000000000003414

25. Ances BM, Vitaliani R, Taylor RA, Liebeskind DS, Voloschin A, Houghton DJ, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain (2005) 128(Pt 8):1764–77. doi: 10.1093/brain/awh526

26. Budhram A, Mirian A, Le C, Hosseini-Moghaddam SM, Sharma M, Nicolle MW. Unilateral cortical FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES): characterization of a distinct clinicoradiographic syndrome. J Neurol (2019) 266(10):2481–7. doi: 10.1007/s00415- 019-09440-8

27. Chihara N, Aranami T, Oki S, Matsuoka T, Nakamura M, Kishida H, et al. Plasmablasts as migratory IgG-producing cells in the pathogenesis of neuromyelitis optica. PloS One (2013) 8(12):e83036. doi: 10.1371/journal.pone.0083036

28. Jacobi AM, Mei H, Hoyer BF, Mumtaz IM, Thiele K, Radbruch A, et al. HLA-DRhigh/CD27high plasmablasts indicate active disease in patients with systemic lupus erythematosus. Ann Rheum Dis (2010) 69(1):305–8. doi: 10.1136/ ard.2008.096495

29. Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, et al. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol (2014) 134(3):679–87. doi: 10.1016/j.jaci.2014.03.034

30. Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA. (2011) 108(9):3701– 6. doi: 10.1073/pnas.1017385108

31. Bennett JL, Lam C, Kalluri SR, Saikali P, Bautista K, Dupree C, et al. Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol (2009) 66(5):617–29. doi: 10.1002/ana.21802

32. Hachiya Y, Uruha A, Kasai-Yoshida E, Shimoda K, Satoh-Shirai I, Kumada S, et al. Rituximab ameliorates anti-N-methyl-D-aspartate receptor encephalitis by removal of short-lived plasmablasts. J Neuroimmunol. (2013) 265(1-2):128–30. doi: 10.1016/j.jneuroim.2013.09.017

33. Malviya M, Barman S, Golombeck KS, Planaguma J, Mannara F, StrutzSeebohm N, et al. NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody. Ann Clin Transl Neurol (2017) 4(11):768–83. doi: 10.1002/ acn3.444

34. Wikenheiser DJ, Stumhofer JS. ICOS Co-stimulation: Friend or foe? Front Immunol (2016) 7:304. doi: 10.3389/fimmu.2016.00304

35. Mak TW, Shahinian A, Yoshinaga SK, Wakeham A, Boucher LM, Pintilie M, et al. Costimulation through the inducible costimulator ligand is essential for both T helper and b cell functions in T cell-dependent b cell responses. Nat Immunol (2003) 4(8):765–72. doi: 10.1038/ni947

36. Xie J, Cui D, Liu Y, Jin J, Tong H, Wang L, et al. Changes in follicular helper T cells in idiopathic thrombocytopenic purpura patients. Int J Biol Sci (2015) 11 (2):220–9. doi: 10.7150/ijbs.10178

37. Seifert M, Kuppers R. Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ b cells and the dynamics of memory b cell generation. J Exp Med (2009) 206(12):2659–69. doi: 10.1084/jem.20091087

38. Seifert M, Przekopowitz M, Taudien S, Lollies A, Ronge V, Drees B, et al. Functional capacities of human IgM memory b cells in early inflammatory responses and secondary germinal center reactions. Proc Natl Acad Sci U S A. (2015) 112(6):E546–55. doi: 10.1073/pnas.1416276112

39. Newell KL, Clemmer DC, Cox JB, Kayode YI, Zoccoli-Rodriguez V, Taylor HE, et al. Switched and unswitched memory b cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration. PloS One (2021) 16(1): e0244855. doi: 10.1371/journal.pone.0244855

40. Carril-Ajuria L, Desnoyer A, Meylan M, Dalban C, Naigeon M, Cassard L, et al. Baseline circulating unswitched memory b cells and b-cell related soluble factors are associated with overall survival in patients with clear cell renal cell carcinoma treated with nivolumab within the NIVOREN GETUG-AFU 26 study. J Immunother Cancer (2022) 10(5):e004885. doi: 10.1136/jitc-2022-004885

41. Iwata S, Tanaka Y. B-cell subsets, signaling and their roles in secretion of autoantibodies. Lupus (2016) 25(8):850–6. doi: 10.1177/0961203316643172

42. Hu F, Zhang W, Shi L, Liu X, Jia Y, Xu L, et al. Impaired CD27(+)IgD(+) b cells with altered gene signature in rheumatoid arthritis. Front Immunol (2018) 9:626. doi: 10.3389/fimmu.2018.00626

43. Leypoldt F, Hoftberger R, Titulaer MJ, Armangue T, Gresa-Arribas N, Jahn H, et al. Investigations on CXCL13 in anti-N-methyl-D-aspartate receptor encephalitis: a potential biomarker of treatment response. JAMA Neurol (2015) 72(2):180–6. doi: 10.1001/jamaneurol.2014.2956

44. Byun JI, Lee ST, Moon J, Jung KH, Sunwoo JS, Lim JA, et al. Distinct intrathecal interleukin-17/interleukin-6 activation in anti-n-methyl-d-aspartate receptor encephalitis. J Neuroimmunol. (2016) 297:141–7. doi: 10.1016/j.jneuroim.2016.05.023

45. Levraut M, Bourg V, Capet N, Delourme A, Honnorat J, Thomas P, et al. Cerebrospinal fluid IL-17A could predict acute disease severity in non-NMDAReceptor autoimmune encephalitis. Front Immunol (2021) 12:673021. doi: 10.3389/fimmu.2021.673021

46. Locci M, Wu JE, Arumemi F, Mikulski Z, Dahlberg C, Miller AT, et al. Activin a programs the differentiation of human TFH cells. Nat Immunol (2016) 17 (8):976–84. doi: 10.1038/ni.3494

47. Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JEJr., et al. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med (1995) 181(5):1755–62. doi: 10.1084/jem.181.5.1755

48. Correale J, Fiol M. Activation of humoral immunity and eosinophils in neuromyelitis optica. Neurology (2004) 63(12):2363–70. doi: 10.1212/ 01.WNL.0000148481.80152.BF

49. Chefdeville A, Treilleux I, Mayeur M-E, Couillault C, Picard G, Bost C, et al. Immunopathological characterization of ovarian teratomas associated with anti-Nmethyl-D-aspartate receptor encephalitis. Acta Neuropathol Commun (2019) 7 (1):1–11. doi: 10.1186/s40478-019-0693-7

50. Makuch M, Wilson R, Al-Diwani A, Varley J, Kienzler AK, Taylor J, et al. Nmethyl-D-aspartate receptor antibody production from germinal center reactions: Therapeutic implications. Ann Neurol (2018) 83(3):553–61. doi: 10.1002/ana.25173

51. Lehmann-Horn K, Irani SR, Wang S, Palanichamy A, Jahn S, Greenfield AL, et al. Intrathecal b-cell activation in LGI1 antibody encephalitis. Neurol Neuroimmunol Neuroinflamm (2020) 7(2):e669. doi: 10.1212/NXI.0000000000000669

52. Dalmau J, Geis C, Graus F. Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. Physiol Rev (2017) 97(2):839–87. doi: 10.1152/physrev.00010.2016

53. Dalmau J, Graus F. Antibody-mediated neuropsychiatric disorders. J Allergy Clin Immunol (2022) 149(1):37–40. doi: 10.1016/j.jaci.2021.11.008

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