Cerebrospinal Fluid IL-17A Could Predict Acute Disease Severity in Non-NMDA-Receptor Autoimmune Encephalitis

Levraut, Michaël; Bourg, V.; Capet, Nicolas; Delourme, Adrien; Honnorat, Jérôme; Thomas, Pierre; Lebrun-Frénay, Christine

doi:10.3389/fimmu.2021.673021

Cited by 16 publications

(17 citation statements)

References 32 publications

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“…Thus, Chemokine (C-X-C motif) ligand 13 (CXCL-13) has been reported as a potential biomarker of treatment response and relapse rate in a bigger cohort of NMDAR-AE patients, but long-term outcomes in relation to CXCL-13 remains to be further elucidated ( 14 ). Similarly, cytokine studies, mostly in NMDAR-AE patients, have suggested particularly Interleukin-17A as a biomarker of disease severity at onset and a poor prognosis ( 15 – 18 ). Limited studies have investigated neuronal surface autoantibody titers as diagnostic or prognostic biomarkers and high titers may indicate poor prognosis and malignancy ( 4 , 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

et al. 2021

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Background and ObjectivesThe two most common autoimmune encephalitides (AE), N-methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE.MethodsPatients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease).ResultsA total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE.DiscussionCSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted.

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Section: Introductionmentioning

confidence: 99%

CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

et al. 2021

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“…In concordance with the scarce inflammatory reaction distinctive of anti-LGI1 encephalitis, only a few studies found significant differences in intrathecal cytokine levels compared to controls. 55 , 56 High CSF levels of CXCL-13 were observed despite an unremarkable CSF analysis, highlighting that a humoral CNS immune response may be present even in the absence of an evident inflammatory CSF. However, serum levels were generally higher, indicating a peripheral synthesis and a subsequent leakage into the CNS.…”

Section: Methodsmentioning

confidence: 97%

Cytokine dynamics and targeted immunotherapies in autoimmune encephalitis

Ciano-Petersen

Muñiz‐Castrillo

Birzu

et al. 2022

Brain Communications

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Autoimmune encephalitides constitute a diverse group of immune-mediated central nervous system disorders mainly characterized by the presence of antibodies targeting neuronal or glial antigens. Despite the notable contribution of antibody discovery to the understanding of their physiopathology, the specific immune cells and inflammatory mediators involved in autoimmune encephalitis are still poorly defined. However, cytokines have recently emerged as crucial signalling molecules in the pathogenesis of autoimmune encephalitis. Cytokines are biologically active, soluble, low-molecular-weight proteins or glycoproteins involved in a wide variety of physiological functions, including central nervous system development and homeostasis, immune surveillance, as well as proliferation and maturation of immune cells. Since unbalanced cytokine expression is considered a hallmark of many autoimmune central nervous system disorders, their identification and quantification has become an essential element in personalized medicine applied to the field of neuroimmunology. Several studies have explored the cytokine profile of autoimmune encephalitis, but their interpretation and comparison is challenging due to their small sample sizes and extremely high heterogeneity, especially regarding the cytokines analysed, type of sample used, and associated neural antibody. Only the cytokine profile of anti-N-methyl-D-aspartate receptor encephalitis has extensively been investigated, with findings suggesting that, although humoral immunity is the main effector, T cells may also be relevant for the development of this disorder. A better understanding of cytokine dynamics governing neuroinflammation might offer the opportunity of developing new therapeutic strategies against specific immune cells, cytokines, antibodies, or intracellular signalling cascades, therefore leading to better outcomes and preventing undesired side effects of the presently used strategies. In this review, we first summarize the current knowledge about the role of cytokines in the pathogenesis of autoimmune encephalitis, combining theoretical analysis with experimental validations, to assess their suitability as clinical biomarkers. Second, we discuss the potential applicability of the novel targeted immunotherapies in autoimmune encephalitis depending on the immunobiology of the associated antibody, their limitations, as well as the main limitations that should be addressed in future studies.

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“…The findings suggested that CSF IL-17A could be useful in determining the severity of AE at the outset. Consequently, CSF IL-17A could be a promising therapeutic target and an effective tool for evaluating early immunosuppressive therapy [ 24 ].…”

Section: Reviewmentioning

confidence: 99%

Utilization of Cerebrospinal Fluid Proteome Analysis in the Diagnosis of Meningioma: A Systematic Review

Choudhary¹,

Elabbas²,

Vyas³

et al. 2021

Cureus

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Meningiomas have been classified as the most commonly occurring primary brain tumors. Although the majority of meningiomas are benign and slow-progressing, the tumors that grow to a larger size are associated with various risks during surgical procedures. Early detection of meningiomas is crucial to the treatment as those detected early can be treated through non-invasive methods. Due to their benign nature, meningiomas contain homogeneous protein biomarkers that can be easily identified. Cerebrospinal fluid (CSF) has a high protein composition which can be used to diagnose various brain tumors. Because CSF comes into direct contact with the brain during its functioning, it is one of the factors that makes it an important source of different biomarkers. An analysis of biochemical changes occurring in the CSF can be useful in assessing the condition of the periventricular white matter and the parenchyma. In this review, PubMed, Medline, PubMed Central, and Google Scholar were used to identify studies discussing meningiomas regarding their assessment, types, diagnosis, and treatment, with more attention directed towards the application of CSF proteome analysis in diagnosis. Priority was given to studies published within the last 15 years. The following keywords were used in the literature search: “cerebrospinal fluid,” “meningiomas,” “brain tumors,” “primary brain tumors,” “protein biomarkers,” “proteome analysis,” and “diagnosis.” Subsequently, the 15 most relevant studies were selected for inclusion in the review. We excluded studies discussing different types of non-brain tumors as well as older articles. The selected studies also underwent a quality appraisal process using corresponding assessment tools. The selected articles were highly informative about meningiomas and the processes of diagnosis and treatment that are currently in use as well as those that are being developed or implemented. The use of CSF proteins in the diagnostic process is also discussed in this review. The studies also describe proteomics as a less invasive procedure that allows for the analysis of entire proteins and the projection of diagnostic images with higher resolutions that aid in the diagnosis.

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Cerebrospinal Fluid IL-17A Could Predict Acute Disease Severity in Non-NMDA-Receptor Autoimmune Encephalitis

Cited by 16 publications

References 32 publications

CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study

Cytokine dynamics and targeted immunotherapies in autoimmune encephalitis

Utilization of Cerebrospinal Fluid Proteome Analysis in the Diagnosis of Meningioma: A Systematic Review

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