Remodelando a neuroimunologia: diagnóstico e tratamento na era da medicina de precisão

dos Passos, Giordani Rodrigues; Adoni, Tarso; Mendes, Maria Fernanda; Sato, Douglas Kazutoshi

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Arquivos de Neuro-Psiquiatria

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Sumário

View and Review • Arq. Neuro-Psiquiatr. 81 (12) • Dez 2023 • https://doi.org/10.1055/s-0043-1777752 copiar

Remodelando a neuroimunologia: diagnóstico e tratamento na era da medicina de precisão

Autoria SCIMAGO INSTITUTIONS RANKINGS

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.

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

Conventional approach	Precision medicine approach
An 18-year-old female presents with transverse myelitis extending from T6 to the conus medullaris and recovers well following intravenous steroids. Retrospectively, she reports an episode suggestive of unilateral optic neuritis at age 16, with spontaneous recovery of visual acuity but with residual dyschromatopsia. Testing for AQP4-IgG results negative and a hypothesis of seronegative NMOSD is made, but she fails to meet the diagnostic criteria. Prednisone and azathioprine are started off-label.	Following the two attacks, the same patient is tested for AQP4-IgG and MOG-IgG using live cell-based assays, with the later coming out positive at high titer. A diagnosis of MOG-IgG-associated disease (MOGAD) is made, and the patient is enrolled into one of the ongoing, phase 3 clinical trials testing selective monoclonal antibodies against either the interleukin-6 receptor (satralizumab) or the neonatal Fc receptor (rozanolixizumab). Serial MOG-IgG testing is performed during follow-up.
A 53-year-old male is admitted to the intensive care unit with a four-week history of symmetric ascending weakness and pain, tremor, ataxia, bilateral facial palsy, and eventually respiratory insufficiency. He receives intravenous immunoglobulin due to suspected GBS. Since his condition continues to deteriorate another four weeks later, CIDP is suspected, and indeed he fulfills the EFNS/PNS electrophysiological diagnostic criteria. However, he fails to respond to intravenous methylprednisolone and then to plasma exchange and is discharged home with tracheostomy and unable to walk.	Soon after admission, the presence of tremor and ataxia prompts testing for IgG antibodies against CASPR1/contactin-1 complex, which come out positive, allowing for a diagnosis of paranodopathy instead of CIDP. Following failure of intravenous immunoglobulin, he receives rituximab (instead of intravenous steroids or plasma exchange) and presents good recovery of respiratory and motor function (requires some help for usual activities, but is able to walk unassisted at discharge).
A 38-year-old female, who had been on teriflunomide since age 32 after receiving a diagnosis of relapsing-remitting MS, presented with a two-week complaint of paroxysmal paresthesia on the left side of her body, including the face, superimposed to increasing fatigue over the past six months. Neurological examination remains unchanged and six-monthly 1.5 Tesla MRI scans of the brain have not shown any new lesions since the start of teriflunomide. Her neurologist suggests the paresthesia may represent a pseudorelapse or a non-organic symptom, given the absence of MRI activity, and explains to her there are no grounds to consider a DMT switch.	To further assess the new symptoms, the treating neurologist orders a 3.0 Tesla MRI of the brain, which shows two paramagnetic rim lesions, and measurements of serum neurofilament light chain, which comes out elevated (Z score = 1.65). She explains to the patient these biomarkers are not yet fully validated, but likely suggest the presence of chronic active disease and increased risk for future disease activity. Taking these findings into account, the neurologist ends up considering the paresthesia as a probable true relapse, in spite of no new MRI lesion, and raises the possibility the worsening fatigue may represent smoldering MS. A shared decision is made to switch to a higher efficacy DMT.

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[1] Address for correspondence Douglas Sato (douglas.sato@pucrs.br)