ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Pain Symptoms in Optic Neuritis.

Signs and symptoms of optic neuritis (ON), an autoimmune disorder of the central nervous system (CNS), differ between patients. Pain, which is commonly reported by ON patients, may be the major reason for some patients to visit the clinic. This article reviews the presence of pain related to ON with respect to underlying disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein associated disease (MOGAD). The aim of this review is to provide an overview of pain symptoms in accordance with the context of various pathophysiological explanations, assist in differential diagnosis of ON patients, especially at the onset of disease, and make recommendations to aid physicians make decisions for follow up diagnostic examinations.

Vision Prognosis and Associated Factors of Optic Neuritis in Dependence of Glial Autoimmune Antibodies.

PURPOSE: To assess the visual prognosis of optic neuritis (ON) in dependence of the glial autoimmune antibody status and associated factors. DESIGN: Longitudinal observational cohort study. METHODS: Patients with ON and measurements of serum concentrations of glial autoantibodies were consecutively and longitudinally examined with a minimal follow-up of 3 months. Patients with multiple sclerosis and double seronegative results were excluded. RESULTS: The study included 529 patients (aquaporin-4 immunoglobulin [AQP4-IgG] seropositive, n = 291; myelin oligodendrocyte glycoprotein immunoglobulin [MOG-IgG] seropositive, n = 112; double-seronegative, n = 126) with 1022 ON episodes (AQP4-IgG seropositive, n = 550; MOG-IgG seropositive, n=254; double-seronegative, n = 218). Prevalence of severe vision loss (best-corrected visual acuity [BCVA] ≤20/200 at the end of follow-up) was higher (P < .001) in the AQP4-IgG group (236/550; 42.9%) than in the seronegative group (68/218; 31.2%) and in the MOG-IgG group (15/254; 5.9%). Prevalence of good vision recovery (BCVA≥20/40) was higher (P < .001) in the MOG-IgG group (229/254; 90.2%) than in the seronegative group (111/218; 50.9%) and in the AQP4-IgG group (236/550; 42.9%). In multivariable logistic analysis, higher prevalence of severe vision loss was associated with AQP4-IgG seropositivity (odds ratio [OR] 1.66; 95% CI 1.14, 2.43; P = .008), male sex (OR 1.97, 95% CI 1.33, 2.93; P < .001), age at ON onset >45 years (OR 1.93, 95% CI 1.35, 2.77; P < .001), nadir vision ≤20/200 (OR 14.11, 95% CI 6.54, 36.93; P < .001), and higher number of recurrences (OR 1.35, 95% CI 1.14, 1.61; P = .001). Higher prevalence of good vision outcome was associated with MOG-IgG seropositivity (OR 8.13, 95% CI 4.82, 14.2; P < .001), age at ON onset <18 years (OR 1.78, 95% CI 1.18, 2.71; P = .006), nadir visual acuity ≥20/40 (OR 4.03; 95% CI 1.45, 14.37; P = .015), and lower number of recurrences (OR 0.60; 95% CI 0.50, 0.72; P < .001). CONCLUSION: Severe vision loss (prevalence in the AQP4-IgG group, MOG-IgG group, and seronegative group: 42.9%, 5.9%, and 31.2%, respectively) was associated with AQP4-IgG seropositivity, male gender, older age at onset, worse nadir vision, and higher number of recurrences.

Clinical predictive factors for diagnosis of MOG-IgG and AQP4-IgG related paediatric optic neuritis: a Chinese cohort study.

BACKGROUND: Different glial-autoantibodies-related paediatric optic neuritis (ON) are associated with different clinical characteristics and prognosis that require different treatments. Because glial autoantibody detection is not available in some parts of the world and there is often a delay in obtaining results, clinical factors that can be used to predict the subtype of paediatric ON are needed. METHODS: This was a single-centre retrospective cohort study. Children who presented with their first ON attack and with complete clinical data were included in the analysis. Single and multiple parameters for predicting paediatric myelin oligodendrocyte glycoprotein immunoglobin-associated ON (MOG-ON) and aquaporin-4 immunoglobin-related ON (AQP4-ON) were calculated. RESULTS: 78 paediatric patients had their first ON attack from January 2016 to December 2019, of whom 69 were included in the final analysis, including 33 MOG-ON cases, 17 AQP4-ON cases and 19 Seronegative-ON cases. For predicting paediatric MOG-ON, the most sensitive predictors were 'male or optic disc swelling (ODS) or bilateral' (sensitivity 0.97 (95% CI 0.82 to 1.00)) and 'follow-up visual acuity (VA) ≤0.1 logMAR or ODS' (sensitivity 0.97 (95% CI 0.82 to 1.00)), and the most specific factor was 'Age ≤11 y and simultaneous CNS involvement' (specificity 0.97 (95% CI 0.84 to 1.00)). For predicting paediatric AQP4-ON, the most sensitive predictor was 'Female or without ODS' (sensitivity 1.00 (95% CI 0.77 to 1.00)), and the most specific factors were Neurological history (sensitivity 0.94 (95% CI 0.83 to 0.98)) and follow-up VA >1.0 logMAR (sensitivity 0.96 (95% CI 0.86 to 0.99)). CONCLUSION: According to our data from a Chinese paediatric cohort, using multiple parameters increases the sensitivity and specificity of diagnosing paediatric MOG-ON and AQP4-ON. These can assist clinicians in diagnosing and treating paediatric ON when glial autoantibody status is not available.

Different alteration patterns of sub-macular choroidal thicknesses in aquaporin-4 immunoglobulin G antibodies sero-positive neuromyelitis optica spectrum diseases and isolated optic neuritis.

PURPOSE: The ocular choroid is a sensitive biomarker of vascular perfusion in optic neuritis (ON) patients due to its vascular structures. The purpose of this study was to evaluate alterations in sub-macular choroidal thicknesses (sub-MCT) in aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) sero-positive neuromyelitis optica spectrum disease (AQP4-IgG+/NMOSD) and isolated ON (ION) patients using optical coherence tomography (OCT). METHODS: A total of 208 ON patients (275 eyes) and healthy controls (HCs) who underwent sub-MCT and retinal microstructure detection with OCT were enrolled in this study. RESULTS: Among all the ON patients, 102 (49.0%) cases were identified as serum AQP4-IgG-positive, with 106 (51.0%) cases being negative, excluding multiple sclerosis as the ION cohort. The sub-MCT in the AQP4-IgG+/NMOSD patients decreased in 0-6 months after ON attacks. However, for the ION cohort, the sub-MCT decreased in 0-2 months and then stayed normal or slightly increased in 2-4 months after the first ON attack, finally sharply decreasing after 6 months. For unilateral AQP4-IgG+/NMOSD patients, eyes without ON also presented retinal layer thinning and sub-MCT slight reduction independent of ON attacks. CONCLUSIONS: The sub-MCT in AQP4-IgG+/NMOSD patients were reduced at all stages of ON, which distinguished the ION patients as decreasing only at chronic stage of ON. It implied that ocular vascular hypoperfusion plays a potential role in ON pathogenesis and the different patterns could be caused by the distinct pathogenesis of AQP4-IgG+/NMOSD and ION.

Effects of experimental N addition on plant diversity in an old-growth temperate forest.

Temperate forest ecosystems have experienced mounting negative effects due to increasing levels of nitrogen (N) deposition. We examined the effects of experimental N addition on plant diversity in an old-growth temperate forest to test the following hypothesis: Long-term excessive N addition decreases plant diversity by affecting the growth of plants, which results from changes in the soil nutrient content and a decrease in the soil pH in temperate forests. Experimental N additions were administered at the following levels since 2008: control (0 kg N ha-1 year-1), low N (30 kg N ha-1 year-1), medium N (60 kg N ha-1 year-1), and high N (120 kg N ha-1 year-1). Additionally, plant diversity was studied from 2014 to 2016. The results showed that the experimental N additions had significant effects on plant diversity and soil properties in an old-growth temperate forest. The high-N treatment decreased the density, cover, and diversity of understory plants, and some herbs even appeared to undergo premature aging, whereas the species diversity of herbs and ferns in the low-N treatment plots showed a slight increasing tendency. This may have been because the old-growth temperate forest is an N-limited ecosystem, so the moderate N input did not show a large influence on plant diversity. However, the long-term high-N treatment ultimately reduced plant diversity by changing the soil nutrient contents, decreasing the pH values, and damaging plant growth. Our results suggested that the long-term excessive N addition negatively affected the forest ecosystem in an N-limited temperature forest.