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CC BY 4.0 · Arq Neuropsiquiatr 2023; 81(12): 1125-1133
DOI: 10.1055/s-0043-1777752
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Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

Remodelando a neuroimunologia: diagnóstico e tratamento na era da medicina de precisão
Giordani Rodrigues dos Passos 
1   Pontifícia Universidade Católica do Rio Grande do Sul, Escola de Medicina e Instituto do Cérebro do Rio Grande do Sul, Porto Alegre RS, Brazil.
,
Tarso Adoni 
2   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo SP, Brazil.
,
Maria Fernanda Mendes 
3   Santa Casa de São Paulo, Faculdade de Ciências Médicas, São Paulo SP, Brazil.
,
Douglas Kazutoshi Sato 
1   Pontifícia Universidade Católica do Rio Grande do Sul, Escola de Medicina e Instituto do Cérebro do Rio Grande do Sul, Porto Alegre RS, Brazil.
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Abstract

Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.

Resumo

A medicina de precisão está revolucionando o campo da neuroimunologia, com uma abordagem inovadora caracterizada pela classificação de doenças com base em sua biologia, compreensão mais profunda dos fatores que levam à heterogeneidade dentro da mesma doença, desenvolvimento de terapias com alvos específicos e estratégias para adaptar as terapias a cada paciente. Esta revisão explora o impacto da medicina de precisão em várias condições neuroimunológicas, incluindo esclerose múltipla (EM), distúrbio do espectro da neuromielite óptica (NMOSD), doença associada ao anticorpo anti-glicoproteína da mielina do oligodendrócito (MOGAD), neurites ópticas, encefalites autoimunes e neuropatias imunomediadas. Discutimos avanços na subclassificação de doenças, reconhecimento de novas entidades, biomarcadores promissores e desenvolvimento de anticorpos monoclonais mais seletivos e imunoterapias de ponta baseadas em células sintéticas para as condições acima. Além disso, analisamos os desafios relacionados com acessibilidade e equidade na implementação dessas tecnologias emergentes, especialmente em ambientes com recursos limitados.

Keywords

Precision Medicine - Autoimmune Diseases of the Nervous System - Multiple Sclerosis - Neuromyelitis Optica - Biomarkers - Immunomodulation - Pharmacogenetics

Palavras-chave

Medicina de Precisão - Doenças Autoimunes do Sistema Nervoso - Esclerose Múltipla - Neuromielite Óptica - Biomarcadores - Imunomodulação - Farmacogenética

Authors' Contributions

All authors provided intellectual contribution to content, helped draft and critically reviewed the manuscript.




Publikationsverlauf

Eingereicht: 02. Oktober 2023

Angenommen: 17. November 2023

Artikel online veröffentlicht:
29. Dezember 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Chitnis T, Prat A. A roadmap to precision medicine for multiple sclerosis. Mult Scler 2020; 26 (05) 522-532
    CrossrefPubMedGoogle Scholar
  • 2 Lublin FD, Reingold SC, Cohen JA. et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83 (03) 278-286
    CrossrefPubMedGoogle Scholar
  • 3 Kuhlmann T, Moccia M, Coetzee T. et al; International Advisory Committee on Clinical Trials in Multiple Sclerosis. Multiple sclerosis progression: time for a new mechanism-driven framework. Lancet Neurol 2023; 22 (01) 78-88
    CrossrefPubMedGoogle Scholar
  • 4 Pitt D, Lo CH, Gauthier SA. et al. Toward Precision Phenotyping of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm 2022; 9 (06) 1-8
    CrossrefPubMedGoogle Scholar
  • 5 Lennon VA, Wingerchuk DM, Kryzer TJ. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364 (9451): 2106-2112
    CrossrefPubMedGoogle Scholar
  • 6 Sato DK, Callegaro D, Lana-Peixoto MA. et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82 (06) 474-481
    CrossrefPubMedGoogle Scholar
  • 7 Kitley J, Waters P, Woodhall M. et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol 2014; 71 (03) 276-283
    CrossrefPubMedGoogle Scholar
  • 8 Banwell B, Bennett JL, Marignier R. et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol 2023; 22 (03) 268-282
    CrossrefPubMedGoogle Scholar
  • 9 Takai Y, Misu T, Fujihara K, Aoki M. Pathology of myelin oligodendrocyte glycoprotein antibody-associated disease: a comparison with multiple sclerosis and aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders. Front Neurol 2023; 14: 1209749
    CrossrefPubMedGoogle Scholar
  • 10 Barreras P, Vasileiou ES, Filippatou AG. et al. Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease. Neurology 2022; 99 (22) e2504-e2516
    CrossrefPubMedGoogle Scholar
  • 11 Jarius S, Paul F, Aktas O. et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J Neuroinflammation 2018; 15 (01) 134
    CrossrefPubMedGoogle Scholar
  • 12 Petzold A, Fraser CL, Abegg M. et al. Diagnosis and classification of optic neuritis. Lancet Neurol 2022; 21 (12) 1120-1134
    CrossrefPubMedGoogle Scholar
  • 13 Binks SNM, Klein CJ, Waters P, Pittock SJ, Irani SR. LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes. J Neurol Neurosurg Psychiatry 2018; 89 (05) 526-534
    CrossrefPubMedGoogle Scholar
  • 14 Graus F, Titulaer MJ, Balu R. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404
    CrossrefPubMedGoogle Scholar
  • 15 Dalmau J, Graus F. Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease. Lancet Neurol 2023; 22 (06) 529-540
    CrossrefPubMedGoogle Scholar
  • 16 Fehmi J, Vale T, Keddie S, Rinaldi S. Nodal and paranodal antibody-associated neuropathies. Pract Neurol 2021; 21: 284-291
    CrossrefPubMedGoogle Scholar
  • 17 Uncini A, Mathis S, Vallat JM. New classification of autoimmune neuropathies based on target antigens and involved domains of myelinated fibres. J Neurol Neurosurg Psychiatry 2022; 93 (01) 57-67 DOI: 10.1136/jnnp-2021-326889.
    CrossrefPubMedGoogle Scholar
  • 18 Calvi A, Haider L, Prados F, Tur C, Chard D, Barkhof F. In vivo imaging of chronic active lesions in multiple sclerosis. Mult Scler 2022; 28 (05) 683-690
    CrossrefPubMedGoogle Scholar
  • 19 Bodini B, Tonietto M, Airas L, Stankoff B. Positron emission tomography in multiple sclerosis - straight to the target. Nat Rev Neurol 2021; 17 (11) 663-675
    CrossrefPubMedGoogle Scholar
  • 20 Bittner S, Oh J, Havrdová EK, Tintoré M, Zipp F. The potential of serum neurofilament as biomarker for multiple sclerosis. Brain 2021; 144 (10) 2954-2963
    CrossrefPubMedGoogle Scholar
  • 21 Ning L, Wang B. Neurofilament light chain in blood as a diagnostic and predictive biomarker for multiple sclerosis: A systematic review and meta-analysis. PLoS One 2022; 17 (09) e0274565
    CrossrefPubMedGoogle Scholar
  • 22 Hauser SL, Bar-Or A, Cohen JA. et al; ASCLEPIOS I and ASCLEPIOS II Trial Groups. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med 2020; 383 (06) 546-557
    CrossrefPubMedGoogle Scholar
  • 23 Waters P, Fadda G, Woodhall M. et al; Canadian Pediatric Demyelinating Disease Network. Serial Anti-Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes. JAMA Neurol 2020; 77 (01) 82-93
    CrossrefPubMedGoogle Scholar
  • 24 Huda S, Whittam D, Jackson R. et al. Predictors of relapse in MOG antibody associated disease: a cohort study. BMJ Open 2021; 11 (11) e055392
    CrossrefPubMedGoogle Scholar
  • 25 Wendel EM, Thonke HS, Bertolini A. et al; BIOMARKER Study Group. Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome. Neurol Neuroimmunol Neuroinflamm 2022; 9 (06) e200035
    CrossrefPubMedGoogle Scholar
  • 26 Jitprapaikulsan J, Fryer JP, Majed M. et al. Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD. Neurol Neuroimmunol Neuroinflamm 2020; 7 (04) e727
    CrossrefPubMedGoogle Scholar
  • 27 Yin HX, Wang YJ, Liu MG. et al. Aquaporin-4 Antibody Dynamics and Relapse Risk in Seropositive Neuromyelitis Optica Spectrum Disorder Treated with Immunosuppressants. Ann Neurol 2023; 93 (06) 1069-1081
    CrossrefPubMedGoogle Scholar
  • 28 Aktas O, Smith MA, Rees WA. et al; N-MOmentum scientific group and the N-MOmentum study investigators. Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker. Ann Neurol 2021; 89 (05) 895-910
    CrossrefPubMedGoogle Scholar
  • 29 Kim H, Lee EJ, Kim S. et al. Longitudinal follow-up of serum biomarkers in patients with neuromyelitis optica spectrum disorder. Mult Scler 2022; 28 (04) 512-521
    CrossrefPubMedGoogle Scholar
  • 30 Dillenseger A, Weidemann ML, Trentzsch K. et al. Digital Biomarkers in Multiple Sclerosis. Brain Sci 2021; 11 (11) 1519
    CrossrefPubMedGoogle Scholar
  • 31 Kulakova OG, Tsareva EY, Lvovs D, Favorov AV, Boyko AN, Favorova OO. Comparative pharmacogenetics of multiple sclerosis: IFN-β versus glatiramer acetate. Pharmacogenomics 2014; 15 (05) 679-685
    CrossrefPubMedGoogle Scholar
  • 32 Zarzuelo Romero MJ, Pérez Ramírez C, Carrasco Campos MI. et al. Therapeutic Value of Single Nucleotide Polymorphisms on the Efficacy of New Therapies in Patients with Multiple Sclerosis. J Pers Med 2021; 11 (05) 335
    CrossrefPubMedGoogle Scholar
  • 33 Díaz-Villamarín X, Piñar-Morales R, Barrero-Hernández FJ, Antúnez-Rodríguez A, Cabeza-Barrera J, Morón-Romero R. Pharmacogenetics of siponimod: A systematic review. Biomed Pharmacother 2022; 153: 113536
    CrossrefPubMedGoogle Scholar
  • 34 Kim S-H, Jeong IH, Hyun JW. et al. Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica: Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab. JAMA Neurol 2015; 72 (09) 989-995
    CrossrefPubMedGoogle Scholar
  • 35 Bennett JL, Aktas O, Rees WA. et al; N-MOmentum study investigators. Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial. EBioMedicine 2022; 86: 104321
    CrossrefPubMedGoogle Scholar
  • 36 Nishimura J, Yamamoto M, Hayashi S. et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med 2014; 370 (07) 632-639
    CrossrefPubMedGoogle Scholar
  • 37 Cree BAC, Bennett JL, Kim HJ. et al; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 2019; 394 (10206): 1352-1363
    CrossrefPubMedGoogle Scholar
  • 38 Yamamura T, Kleiter I, Fujihara K. et al. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med 2019; 381 (22) 2114-2124
    CrossrefPubMedGoogle Scholar
  • 39 Traboulsee A, Greenberg BM, Bennett JL. et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol 2020; 19 (05) 402-412
    CrossrefPubMedGoogle Scholar
  • 40 Pittock SJ, Berthele A, Fujihara K. et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med 2019; 381 (07) 614-625
    CrossrefPubMedGoogle Scholar
  • 41 Pittock SJ, Barnett M, Bennett JL. et al. Ravulizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. Ann Neurol 2023; 93 (06) 1053-1068
    CrossrefPubMedGoogle Scholar
  • 42 Pittock SJ, Zekeridou A, Weinshenker BG. Hope for patients with neuromyelitis optica spectrum disorders - from mechanisms to trials. Nat Rev Neurol 2021; 17 (12) 759-773
    CrossrefPubMedGoogle Scholar
  • 43 Krämer J, Bar-Or A, Turner TJ, Wiendl H. Bruton tyrosine kinase inhibitors for multiple sclerosis. Nat Rev Neurol 2023; 19 (05) 289-304
    CrossrefPubMedGoogle Scholar
  • 44 Martin E, Aigrot MS, Grenningloh R. et al. Bruton's Tyrosine Kinase Inhibition Promotes Myelin Repair. Brain Plast 2020; 5 (02) 123-133
    CrossrefPubMedGoogle Scholar
  • 45 Dybowski S, Torke S, Weber MS, Targeting B. Targeting B Cells and Microglia in Multiple Sclerosis With Bruton Tyrosine Kinase Inhibitors: A Review. JAMA Neurol 2023; 80 (04) 404-414
    CrossrefPubMedGoogle Scholar
  • 46 Montalban X, Arnold DL, Weber MS. et al; Evobrutinib Phase 2 Study Group. Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis. N Engl J Med 2019; 380 (25) 2406-2417
    CrossrefPubMedGoogle Scholar
  • 47 Reich DS, Arnold DL, Vermersch P. et al; Tolebrutinib Phase 2b Study Group. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2021; 20 (09) 729-738
    CrossrefPubMedGoogle Scholar
  • 48 von Baumgarten L, Stauss HJ, Lünemann JD. Synthetic Cell-Based Immunotherapies for Neurologic Diseases. Neurol Neuroimmunol Neuroinflamm 2023; 10 (05) e200139
    CrossrefPubMedGoogle Scholar
  • 49 Granit V, Benatar M, Kurtoglu M. et al; MG-001 Study Team. Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. Lancet Neurol 2023; 22 (07) 578-590
    CrossrefPubMedGoogle Scholar
  • 50 Qin C, Tian DS, Zhou LQ. et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduct Target Ther 2023; 8 (01) 5
    CrossrefPubMedGoogle Scholar
  • 51 Gupta S, Simic M, Sagan SA. et al. CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity. Neurol Neuroimmunol Neuroinflamm 2023; 10 (02) e200080
    CrossrefPubMedGoogle Scholar
  • 52 Lu CY, Terry V, Thomas DM. Precision medicine: affording the successes of science. NPJ Precis Oncol 2023; 7 (01) 3
    CrossrefPubMedGoogle Scholar
  • 53 Khoury MJ, Bowen S, Dotson WD. et al. Health equity in the implementation of genomics and precision medicine: A public health imperative. Genet Med 2022; 24 (08) 1630-1639
    CrossrefPubMedGoogle Scholar
  • 54 Rocha CS, Secolin R, Rodrigues MR, Carvalho BS, Lopes-Cendes I. The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations. NPJ Genom Med 2020; 5: 42
    CrossrefPubMedGoogle Scholar