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Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production. Cotzomi Elizabeth,Stathopoulos Panos,Lee Casey S,Ritchie Alanna M,Soltys John N,Delmotte Fabien R,Oe Tyler,Sng Joel,Jiang Ruoyi,Ma Anthony K,Vander Heiden Jason A,Kleinstein Steven H,Levy Michael,Bennett Jeffrey L,Meffre Eric,O'Connor Kevin C Brain : a journal of neurology Neuromyelitis optica spectrum disorders (NMOSD) constitute rare autoimmune disorders of the CNS that are primarily characterized by severe inflammation of the spinal cord and optic nerve. Approximately 75% of NMOSD patients harbour circulating pathogenic autoantibodies targeting the aquaporin-4 water channel (AQP4). The source of these autoantibodies remains unclear, but parallels between NMOSD and other autoantibody-mediated diseases posit compromised B cell tolerance checkpoints as common underlying and contributing factors. Using a well established assay, we assessed tolerance fidelity by creating recombinant antibodies from B cell populations directly downstream of each checkpoint and testing them for polyreactivity and autoreactivity. We examined a total of 863 recombinant antibodies. Those derived from three anti-AQP4-IgG seropositive NMOSD patients (n = 130) were compared to 733 antibodies from 15 healthy donors. We found significantly higher frequencies of poly- and autoreactive new emigrant/transitional and mature naïve B cells in NMOSD patients compared to healthy donors (P-values < 0.003), thereby identifying defects in both central and peripheral B cell tolerance checkpoints in these patients. We next explored whether pathogenic NMOSD anti-AQP4 autoantibodies can originate from the pool of poly- and autoreactive clones that populate the naïve B cell compartment of NMOSD patients. Six human anti-AQP4 autoantibodies that acquired somatic mutations were reverted back to their unmutated germline precursors, which were tested for both binding to AQP4 and poly- or autoreactivity. While the affinity of mature autoantibodies against AQP4 ranged from modest to strong (Kd 15.2-559 nM), none of the germline revertants displayed any detectable binding to AQP4, revealing that somatic hypermutation is required for the generation of anti-AQP4 autoantibodies. However, two (33.3%) germline autoantibody revertants were polyreactive and four (66.7%) were autoreactive, suggesting that pathogenic anti-AQP4 autoantibodies can originate from the pool of autoreactive naïve B cells, which develops as a consequence of impaired early B cell tolerance checkpoints in NMOSD patients. 10.1093/brain/awz106
The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Höftberger Romana,Guo Yong,Flanagan Eoin P,Lopez-Chiriboga A Sebastian,Endmayr Verena,Hochmeister Sonja,Joldic Damir,Pittock Sean J,Tillema Jan Mendelt,Gorman Mark,Lassmann Hans,Lucchinetti Claudia F Acta neuropathologica We sought to define the pathological features of myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) in an archival autopsy/biopsy cohort. We histopathologically analyzed 2 autopsies and 22 brain biopsies from patients with CNS inflammatory demyelinating diseases seropositive for MOG-antibody by live-cell-based-assay with full length MOG in its conformational form. MOGAD autopsies (ages 52 and 67) demonstrate the full spectrum of histopathological features observed within the 22 brain biopsies (median age, 10 years; range, 1-66; 56% female). Clinical, radiologic, and laboratory characteristics and course (78% relapsing) are consistent with MOGAD. MOGAD pathology is dominated by coexistence of both perivenous and confluent white matter demyelination, with an over-representation of intracortical demyelinated lesions compared to typical MS. Radially expanding confluent slowly expanding smoldering lesions in the white matter as seen in MS, are not present. A CD4+ T-cell dominated inflammatory reaction with granulocytic infiltration predominates. Complement deposition is present in all active white matter lesions, but a preferential loss of MOG is not observed. AQP4 is preserved, with absence of dystrophic astrocytes, and variable oligodendrocyte and axonal destruction. MOGAD is pathologically distinguished from AQP4-IgG seropositive NMOSD, but shares some overlapping features with both MS and ADEM, suggesting a transitional pathology. Complement deposition in the absence of selective MOG protein loss suggest humoral mechanisms are involved, however argue against endocytic internalization of the MOG antigen. Parallels with MOG-EAE suggest MOG may be an amplification factor that augments CNS demyelination, possibly via complement mediated destruction of myelin or ADCC phagocytosis. 10.1007/s00401-020-02132-y
Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Reindl Markus,Waters Patrick Nature reviews. Neurology Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease. 10.1038/s41582-018-0112-x
Simultaneous bilateral optic neuritis in China: clinical, serological and prognostic characteristics. Kang Hao,Liu Zihao,Li Hongyang,Chen Tingjun,Ai Nanping,Xu Quangang,Cao Shanshan,Tao Yong,Wei Shihui Acta ophthalmologica PURPOSE:To analyse the clinical characteristics of simultaneous bilateral ON patients in China. METHODS:This retrospective study was done on 51 primary bilateral ON patients between April 2008 and July 2016 at the Chinese People's Liberation Army General Hospital. Fifty eight primary unilateral ON patients formed the control group. Demographic data, clinical course, serum autoantibody status, connective tissue disorders, magnetic resonance imaging and visual functions were compared. RESULTS:The mean age at disease onset in the bilateral group was younger than that of the unilateral group (p = 0.001). Cerebrospinal fluid (CSF) total cell count and CSF total protein were significantly higher in the bilateral group (p = 0.001, p = 0.025). Aquaporin-4 (AQP4) antibodies were detected in 39% and 21% of the bilateral and unilateral patients, respectively (p = 0.03). Twenty two percent of the bilateral patients fulfilled the diagnosis of neuromyelitis optica (NMO); 7% in the unilateral group did so (p = 0.03). Serum autoantibodies (ANA, SSA, SSB, etc.) were found in 49% of the bilateral patients and 29% of the unilateral patients (p = 0.035). After treatment, the bilateral patients were significantly more prone to severe visual disability eventually than their unilateral counterparts (p = 0.002). Patients with MOG-IgG (myelin oligodendrocyte glycoprotein-IgG) represented 26% of the patients negative for AQP4-IgG. Myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) sero-positive patients were more likely to recover than the other patients (p < 0.001). CONCLUSION:Simultaneous bilateral ON is a severe disorder closely related to serum AQP4-IgG and MOG-IgG, which are more likely to involve younger people and incur severe visual disability eventually. Myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) sero-positive patients have higher risk of ON relapses and better visual prognosis. 10.1111/aos.14013
Optic neuritis: the eye as a window to the brain. Jenkins Thomas M,Toosy Ahmed T Current opinion in neurology PURPOSE OF REVIEW:Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease. RECENT FINDINGS:We will present a practical approach to assessment of optic neuritis, highlighting the role of optical coherence tomography, when to test for new antibodies and the results of recent trials of sodium channel blockers. SUMMARY:Optic neuritis remains a clinical diagnosis; increasingly optical coherence tomography is a key ancillary investigation. Patients with 'typical' optic neuritis, commonly a first presentation of multiple sclerosis, must be distinguished from 'atypical' optic neuritis, who require testing for new pathological antibodies and require more aggressive-targeted treatment. Sodium channel blockade is an emerging and novel potential therapeutic pathway in neuroinflammatory disease. 10.1097/WCO.0000000000000414
Longitudinal Assessment of Transorbital Sonography, Visual Acuity, and Biomarkers for Inflammation and Axonal Injury in Optic Neuritis. Lochner Piergiorgio,Cantello Roberto,Fassbender Klaus,Lesmeister Martin,Nardone Raffaele,Siniscalchi Antonio,Clemente Nausicaa,Naldi Andrea,Coppo Lorenzo,Brigo Francesco,Comi Cristoforo Disease markers BACKGROUND AND OBJECTIVE:To investigate the relationship between optic nerve sheath diameter, optic nerve diameter, visual acuity and osteopontin, and neurofilament heavy chain in patients with acute optic neuritis. PATIENTS AND METHODS:Sonographic and visual acuity assessment and biomarker measurements were executed in 23 patients with unilateral optic neuritis and in 19 sex- and age-matched healthy controls. RESULTS:ONSD was thicker on the affected side at symptom onset (median 6.3 mm; interquartile range 6.0-6.5) than after 12 months (5.3 mm; 4.9-5.6; < 0.001) or than in controls (5.2 mm; 4.8-5.5; < 0.001). OND was significantly increased in the affected side (3.4 mm; 2.9-3.8) compared to healthy controls (2.7 mm; 2.5-2.9; < 0.001) and was thicker at baseline than after 12 months (2.8 mm; 2.7-3.0; < 0.01). Visual acuity improved significantly after 12 months (1.00; 0.90-1.00) compared to onset of symptoms (0.80; 0.40-1.00; < 0.001). OPN levels were significantly higher in patients at presentation (median 6.44 ng/ml; 2.05-10.06) compared to healthy controls (3.21 ng/ml, 1.34-4.34; < 0.03). Concentrations of NfH were significantly higher in patients than in controls. CONCLUSION:ONSD and OND are increased in the affected eye. OPN and NfH are elevated in patients, confirming the presence of any underlying inflammation and axonal injury. 10.1155/2017/5434310
Visual Evoked Potentials as a Biomarker in Multiple Sclerosis and Associated Optic Neuritis. Leocani Letizia,Guerrieri Simone,Comi Giancarlo Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society : ABSTRACT:: Multiple sclerosis (MS) is an inflammatory, degenerative disease of the central nervous system (CNS) characterized by progressive neurological decline over time. The need for better "biomarkers" to more precisely capture and track the effects of demyelination, remyelination, and associated neuroaxonal injury is a well-recognized challenge in the field of MS. To this end, visual evoked potentials (VEPs) have a role in assessing the extent of demyelination along the optic nerve, as a functionally eloquent CNS region. Moreover, VEPs testing can be used to predict the extent of recovery after optic neuritis (ON) and capture disabling effects of clinical and subclinical demyelination events in the afferent visual pathway. In this review, the evolving role of VEPs in the diagnosis of patients with ON and MS and the utility of VEPs testing in determining therapeutic benefits of emerging MS treatments is discussed. 10.1097/WNO.0000000000000704
Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis. Modvig S,Degn M,Sander B,Horwitz H,Wanscher B,Sellebjerg F,Frederiksen J L Multiple sclerosis (Houndmills, Basingstoke, England) BACKGROUND:Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE:The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. METHODS:We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses. RESULTS:CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (β=13.8, p=0.0008), RNFL (β=5.6, p=0.0004) and GC-IPL (β=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (β=12.9, p=0.0021 for NF-L, β=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CONCLUSION:CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements. 10.1177/1352458515599074
Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study. Olesen M N,Soelberg K,Debrabant B,Nilsson A C,Lillevang S T,Grauslund J,Brandslund I,Madsen J S,Paul F,Smith T J,Jarius S,Asgari N Journal of neuroinflammation BACKGROUND:Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. METHODS:Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19-41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2-38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons ("q"). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. RESULTS:CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r > 0.69 and p < 0.002) and IgG index (r > 0.55, p < 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p < 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one ("candidate") and IgG index, OCB, and leukocytes in another ("routine"). Area under the curve was 0.89 [95% CI 0.77-1] and 0.86 [0.74-0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. CONCLUSIONS:CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS. 10.1186/s12974-019-1440-5
Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients. Disease markers BACKGROUND:Multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the central nervous system, typically features immune-mediated focal demyelination and secondary axonal degeneration. Cerebral hypoperfusion of the normal-appearing white matter (NAWM) has been reported in MS patients and may be mediated by elevated levels of endothelin-1 (ET-1), a most potent vasoconstrictive peptide released from reactive astrocytes in MS focal lesions. Optic neuritis (ON) is one of the most frequent manifestations of MS and also shows peripapillary vascular hypoperfusion in combination with disc swelling. AIMS:We aimed to compare serum and cerebrospinal fluid (CSF) levels of ET-1 as a potential prognostic marker of MS-ON in two groups of patients differing for severity of MS-ON clinical presentation. MATERIALS AND METHODS:A cross-sectional study to compare serum and CSF levels of ET-1 between patients with clinically aggressive MS-ON (A-MS-ON) and nonaggressive MS-ON (NA-MS-ON) according to conventional ophthalmological criteria, including optical coherence tomography. CSF and serum concentrations of ET-1 were measured using a commercially available ELISA method. RESULTS:Sixteen patients consecutively referred to the Units of Neurology for visual disturbances attributable to MS were recruited, 11 (69%) patients with A-MS-ON and 5 (31%) with NA-MS-ON. Median CSF ET-1 levels and CSF/serum ET-1 quotient were significantly higher in patients with A-MS-ON (0.30 vs. 0.56 ng/ml) as compared to NA-MS-ON (0.16 vs. 0.16). CONCLUSIONS:Severity and failure in the recovery from ON in MS patients may depend from vascular hypoperfusion of the optic nerve induced by high intrathecally produced ET-1, a potential prognostic marker of ON recovery in MS. The detection of CSF ET-1 levels may allow identifying groups of ON patients potentially benefitting from treatment with ET-1 antagonists (e.g., bosentan). 10.1155/2019/9320791
[A case of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-N-methyl-D-aspartate (NMDA) receptor antibody-positive encephalitis with optic neuritis]. Nagata Satoshi,Nishimura Yuji,Mitsuo Kunihiko Rinsho shinkeigaku = Clinical neurology A 20-year-old female was hospitalized due to generalized seizure two weeks after an infection. She reported disorientation, neck stiffness and weakness in her legs. MRI FLAIR images and TWI on her first visit to our hospital showed hyperintense lesions in the bilateral cingulate gyrus and the medial region of the superior frontal gyrus. Gadolinium (Gd)-enhanced TWI showed enhancement in the upper part of the corpus callosum. Examination of her cerebrospinal fluid (CSF) revealed mildly elevated leucocytes. After the administration of high-dose intravenous methylprednisolone, her symptoms partially improved. However, MRI TWI at 16 days after admission showed a lesion with a peripheral hypointense rim in the left side of the cingulate gyrus, which had ring enhancement on contrast CT. FLAIR images at 28 days after admission showed the hyperintense lesion spreading in the subcallosal area and the brainstem, and coronal short inversion time inversion recovery (STIR) images demonstrated bilateral optic neuritis. She was treated with steroid pulse therapy and plasma exchange. Thereafter her symptoms improved. The patient's CSF at 27 days after admission tested positive for anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies and anti-N-methyl-D-aspartate (anti-NMDA) receptor antibodies. Encephalitis with optic neuritis in a patient with both anti-MOG and anti-NMDA receptor antibodies is very rare. Coexistence of multiple antibodies in the same patient may contribute to the diversity of autoimmune diseases associated with anti-MOG antibodies or anti-NMDA receptor antibodies. 10.5692/clinicalneurol.cn-001194
Optic neuritis in the era of biomarkers. Chen John J,Pittock Sean J,Flanagan Eoin P,Lennon Vanda A,Bhatti M Tariq Survey of ophthalmology The Optic Neuritis Treatment Trial, a landmark study completed in 1991, stratified the risk of multiple sclerosis in patients with optic neuritis. Since that time, unique biomarkers for optic neuritis have been found. The antibody against aquaporin-4 (AQP4)-immunoglobulin G (IgG) discovered in 2004 was found to be both the pathologic cause and a reliable biomarker for neuromyelitis optica spectrum disorders. This finding enabled an expanded definition of the phenotype of neuromyelitis optica spectrum disorder and improved treatment of the disease. Subsequently, myelin oligodendrocyte glycoprotein (MOG) IgG was recognized to be a marker for MOG-IgG-associated disorder, a central demyelinating disease characterized by recurrent optic neuritis, prominent disk edema, and perineural optic nerve enhancement on magnetic resonance imaging. Most multiple sclerosis disease-modifying agents are ineffective for AQP4-IgG-positive neuromyelitis optica spectrum disorder and MOG-IgG-associated disorder. Because there are crucial differences in treatment and prognosis between multiple sclerosis, AQP4-IgG-positive neuromyelitis optica spectrum disorder, and MOG-IgG-associated disorder, ophthalmologists should be aware of these new biomarkers of optic neuritis and incorporate their testing in all patients with atypical optic neuritis. 10.1016/j.survophthal.2019.08.001
Clinical usefulness of prognostic biomarkers in optic neuritis. Tejeda-Velarde A,Costa-Frossard L,Sainz de la Maza S,Carrasco Á,Espiño M,Picón C,Toboso I,Walo P E,Lourido D,Muriel A,Álvarez-Cermeño J C,Villar L M European journal of neurology BACKGROUND AND PURPOSE:Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis. METHODS:Sixty-eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid-specific oligoclonal IgM bands (LS-OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored. RESULTS:The mean time of follow-up of our series was 46.4 months. Twenty-five patients (36.7%) developed CDMS during follow-up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS-OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001). CONCLUSIONS:Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS-OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions. 10.1111/ene.13553
Elevation of AQP4 and selective cytokines in experimental autoimmune encephalitis mice provides some potential biomarkers in optic neuritis and demyelinating diseases. Sun Li,Weng Huan,Li Zhenxin International journal of clinical and experimental pathology Idiopathic optic neuritis (ION) is an inflammation of the optic nerve that may result in a complete or partial loss of vision. ION is usually due to the immune attack of the myelin sheath covering the optic nerve. ION acts frequently as the first symptoms of multiple sclerosis (MS) and neuromyelitis optica (NMO), or other inflammatory demyelinating disorders. The pathogenic progression of ION remains unclear. Experimental autoimmune encephalitis (EAE) is a commonly used model of idiopathic inflammatory demyelinating disorders (IIDDs); the optic nerve is affected in EAE as well. The specific mediators of demyelination in optic neuritis are unknown. Recent studies have indicated what T-cell activation in peripheral blood is associated with optic neuritis pathogenesis. The object of the present study was to determine whether certain cytokines (IL-6, IL-17A, and IL-23) and AQP4 contribute to the demyelinating process using EAE model. We have found that IL-6R, AQP4 and IL-23R are significantly increased in mRNA and protein levels in optic nerves in EAE mice compared to control mice; serum AQP4, IL-6, IL-17A, IL-23 are increased whereas transforming growth factor beta (TGF-β) is decreased in EAE mice. These results suggest that AQP4 and selective cytokines in serum are associated with ION pathogenesis in the animal model, and these results shine light for future clinical diagnosis as potential biomarkers in ION patients.