The poor recovery of neuromyelitis optica spectrum disorder is associated with a lower level of CXCL12 in the human brain

Kang, Hanyujie; Cao, Shanshan; Chen, Tingjun; Jiang, Zhaocai; Liu, Zihao; Li, Zhaohui; Wei, Yangang; Ai, Nanping; Xu, Quangang; Lin, Qing; Wei, Shihui

doi:10.1016/j.jneuroim.2015.10.005

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…However, in patients with anti-AQP4-IgG, pulmonary and gastric symptoms have not been described. Yet there are studies investigating binding of patients' anti-AQP4-IgG against two of the major AQP4 forms expressed on astrocytes (59), although others have proposed that anti-AQP4-IgG may not be the main direct cause of the astrocytopathy in NMOSD, but demonstrated that anti-AQP4-IgG down-regulates CXC motif ligand 12 (CXCL12) and impairs remyelination by oligodendrocyte progenitor cells (60). Indeed, the high degree of heterogeneity of the patients' IgGs to targeting different isoforms of AQP4 raises the question how well other isoforms are targeted, especially in non-CNS organs.…”

Section: Discussionmentioning

confidence: 99%

Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

et al. 2021

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Background: Neuromyelitis optica spectrum disorder (NMOSD) is a clinically defined, inflammatory central nervous system (CNS) disease of unknown cause, associated with humoral autoimmune findings such as anti-aquaporin 4 (AQP4)-IgG. Recent clinical trials showed a benefit of anti-B cell and anti-complement-antibodies in NMOSD, suggesting relevance of anti-AQP4-IgG in disease pathogenesis.Objective: AQP4-IgG in NMOSD is clearly defined, yet up to 40% of the patients are negative for AQP4-IgG. This may indicate that AQP4-IgG is not disease-driving in NMOSD or defines a distinct patient endotype.Methods: We established a biobank of 63 clinically well-characterized NMOSD patients with an extensive annotation of 351 symptoms, patient characteristics, laboratory results and clinical scores. We used phylogenetic clustering, heatmaps, principal component and longitudinal causal interference analyses to test for the relevance of anti-AQP4-IgG.Results: Anti-AQP4-IgG was undetectable in 29 (46%) of the 63 NMOSD patients. Within anti-AQP4-IgG-positive patients, anti-AQP4-IgG titers did not correlate with clinical disease activity. Comparing anti-AQP4-IgG-positive vs. -negative patients did not delineate any clinically defined subgroup. However, anti-AQP4-IgG positive patients had a significantly (p = 0.022) higher rate of additional autoimmune diagnoses.Conclusion: Our results challenge the assumption that anti-AQP4-IgG alone plays a disease-driving role in NMOSD. Anti-AQP4-IgG might represent an epiphenomenon associated with NMOSD, may represent one of several immune mechanisms that collectively contribute to the pathogenesis of this disease or indeed, anti-AQP4-IgG might be the relevant factor in only a subgroup of patients.

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Section: Discussionmentioning

confidence: 99%

Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

et al. 2021

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“…However, while GFAP levels rapidly return to normal following treatment for an NMOSD attack, MBP remains high, suggesting that despite the acutely predominant astrocytic damage in NMOSD, active demyelination persists for longer [ 115 ]. Furthermore, AQP4-IgG-positive individuals demonstrate the downregulation of CXC-motif ligand 12(CXCL12), a chemokine protein released by astrocytes that plays a role in the activation of OPCs to promote remyelinating processes [ 116 ]. A more recent study found that NFL levels are higher in patients with NMOSD in comparison with MS and MOGAD suggesting prominent axonal injury in NMOSD .…”

Section: Reparative and Remyelination Therapiesmentioning

confidence: 99%

Symptomatic and restorative therapies in neuromyelitis optica spectrum disorders

et al. 2021

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Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune inflammatory conditions that primarily target the optic nerves, spinal cord, brainstem, and occasionally the cerebrum. NMOSD is characterized by recurrent attacks of visual, motor, and/or sensory dysfunction that often result in severe neurological deficits. In recent years, there has been a significant progress in relapse treatment and prevention but the residual disability per attack remains high. Although symptomatic and restorative research has been limited in NMOSD, some therapeutic approaches can be inferred from published case series and evidence from multiple sclerosis literature. In this review, we will discuss established and emerging therapeutic options for symptomatic treatment and restoration of function in NMOSD. We highlight NMOSD-specific considerations and identify potential areas for future research. The review covers pharmacologic, non-pharmacologic, and neuromodulatory approaches to neuropathic pain, tonic spasms, muscle tone abnormalities, sphincter dysfunction, motor and visual impairment, fatigue, sleep disorders, and neuropsychological symptoms. In addition, we briefly discuss remyelinating agents and mesenchymal stem cell transplantation in NMOSD.

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“…Se ha observado que los títulos de IgG-AQP4 muestran una correlación positiva, más fuerte con actividad de la enfermedad antes de las recaídas que durante la remisión (11). Sin embargo, la IgG-AQP4 sérica no es un indicador preciso de la gravedad de la astrocitopatía (12).…”

Section: U J E R C O N D I a G N ó S T I C O D E N O V O …unclassified

Mujer con diagnóstico de novo de espectro de neuromielitis óptica con anticuerpos para AQP4 positivo. Un Reporte de Caso

2021

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Introducción: Presentamos el caso de una paciente de 55 años de edad, con antecedente de hipertensión arterial, quien presentó un cuadro de deterioro visual bilateral de 2 meses de evolución, con posterior presencia de un síndrome motor y sensitivo del hemicuerpo derecho asociado a compromiso de tórax y abdomen; las imágenes de resonancia magnética (RM) de cerebro, orbitas, columna cervical y torácica simple y con medio de contraste mostraron una neuritis óptica bilateral severa, asociado a mielopatía cervical longitudinalmente extensa de carácter inflamatorio, hallazgos sugestivos de un espectro de neuromielitis óptica (NMO), por lo que se llevó a toma de punción lumbar que mostró un líquido cefalorraquideo (LCR) con pleocitosis neutrofílica, AQP4 positiva, glucosa y proteínas normales. Recibió manejo con corticoides a altas dosis asociado a plasmaféresis con mejoría parcial de los síntomas; posteriormente se dio de alta, para inicio de manejo inmunomodulador con Rituximab, de forma ambulatoria. Objetivo: Describir un caso y las características clínicas generadas en una paciente con neuromielitis óptica, su diagnóstico, tratamiento, evolución y pronóstico. Método: Se realizó una revisión de la historia clínica y extracción de datos previa firma de consentimiento informado, posteriormente se hizo una búsqueda de artículos de revisión bibliográfica en PubMed, SCIELO, ProQuest, usando descriptores de Ciencias de la Salud (DeCs) y términos MeSH: reportes de caso, publicaciones y revisiones. Se usaron artículos comprendidos entre 2006 al 2018. Resultados: Se documentó la presentación clínica, el diagnóstico, evolución y tratamiento de acuerdo con el manejo dado. Discusión: Al enfrentarnos a un cuadro de una paciente con neuromielitis óptica, podemos encontrar diferentes espectros clínicos, evolución y respuestas al tratamiento.

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The poor recovery of neuromyelitis optica spectrum disorder is associated with a lower level of CXCL12 in the human brain

Cited by 11 publications

References 36 publications

Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

Anti-aquaporin 4 IgG Is Not Associated With Any Clinical Disease Characteristics in Neuromyelitis Optica Spectrum Disorder

Symptomatic and restorative therapies in neuromyelitis optica spectrum disorders

Mujer con diagnóstico de novo de espectro de neuromielitis óptica con anticuerpos para AQP4 positivo. Un Reporte de Caso

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