A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. RESULTS: Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. CONCLUSIONS: MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

Decreased kynurenine in cerebrospinal fluid and potential role in neuromyelitis optica spectrum disorder.

Tryptophan (Trp) metabolism has been implicated in neuroinflammatory and neurodegenerative disorders, but its relationship with neuromyelitis optica spectrum disorder (NMOSD) is unclear. In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases and 6 neurometabolites in the tryptophan metabolic pathway, including 5-hydroxytryptamine (5-HT), kynurenine (KYN), melatonin (MLT), 5-hydroxyindoleacetic acid (5HIAA), 3-hydroxy-o-aminobenzoic acid (3-HAA), and kynurenic acid (KYA), were measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD-IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD-IgG specifically recognized KYN, which reversed the NMOSD-IgG-induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4-IgG-positive NMOSD patients.

Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

Serum neurofilament light chain in adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disease: Correlation with relapses and seizures.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty-nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat-sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single-molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: ß = 2.02, p = 0.003), seizures (multivariate: ß = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: ß = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.

Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants.

BACKGROUND: Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD. METHODS: Through questionnaires in four medical centres in 2016-2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted. RESULTS: The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues. CONCLUSION: Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD.

Whole-exome sequencing reveals the major genetic factors contributing to neuromyelitis optica spectrum disorder in Chinese patients with aquaporin 4-IgG seropositivity.

BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)-IgG seropositivity. METHODS: Whole-exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4-IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen (HLA) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted. RESULTS: A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1. HLA sequencing confirmed that the most significant allele was HLA-DQB1*05:02 (p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA-DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model (p < 0.05). The proportion of haplotype "HLA-DQB1*05:02-DRB1*15:01" was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively (p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss-of-function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1-G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls (p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes. CONCLUSIONS: Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1-G390R play important roles in disease susceptibility.

Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort.

OBJECTIVE: Myelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus. METHODS: HLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG). RESULTS: Paediatric-onset MOGAD was associated with the DQB1*05:02-DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02-DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA-peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen-antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele. CONCLUSIONS: This study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.

Relapsing optic neuritis and meningoencephalitis in a child: case report of delayed diagnosis of MOG-IgG syndrome.

BACKGROUND: Recurrent optic neuritis (ON) was previously thought to be associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Meningoencephalitis has recently been suggested to be a clinical finding typical of myelin oligodendrocyte glycoprotein (MOG) encephalomyelitis. We report a Chinese patient with recurrent ON at disease initiation, who had a delayed diagnosis of MOG-IgG syndrome, until recurrent meningoencephalitis appeared and serum MOG-IgG was detected. CASE PRESENTATION: From the age of 7 years, an AQP4-IgG negative female patient had 10 disease recurrences, including 4 episodes of recurrent ON, 4 episodes of fever and meningoencephalitis, and 2 episodes of ON as well as meningoencephalitis. She was initially diagnosed as recurrent ON and treated with glucocorticoids followed by gradual tapering when ON reoccurred. Later, she was diagnosed as central nervous system infection when fever and meningoencephalitis appeared, and antiviral drugs and glucocorticoids were used. However, when she returned to our department for follow-up on July 2017, the results of serum demyelinating autoimmune antibody revealed positive MOG-IgG (titer 1:320 by an in-house, cell-based assay using live cells transfected with full-length human MOG). A diagnosis of MOG-IgG syndrome was established. CONCLUSIONS: Testing for MOG-IgG in atypical MS and NMOSD patients, and patients with meningoencephalitis with a history of relapsing demyelinating symptoms is warranted.

Cerebrospinal Fluid Level of Soluble CD27 Is Associated with Disease Severity in Neuromyelitis Optica Spectrum Disorder.

OBJECT: CD27 belongs to the tumor necrosis factor receptor family and is constitutively expressed on T cells. The concentration of cerebrospinal fluid (CSF) soluble (s)CD27 is elevated in patients with multiple sclerosis (MS). However, whether the level of CSF sCD27 is elevated in neuromyelitis optica spectrum disorder (NMOSD) remains unknown. The aim of this study was to measure the CSF concentration of sCD27 and to determine its relationship with NMOSD disease activity. METHODS: CSF CXCL13 was measured by ELISA in neuromyelitis optica (NMO) (n = 31) and MS (n = 23) patients and in controls (CTLs) (n = 22). RESULTS: The concentration of sCD27 was higher in the NMO group than in the MS (p = 0.082) and CTL (p = 0.002) groups, and there was a positive correlation with CSF IL-6 (p = 0.000) and a negative correlation with IL-10 (p = 0.073). In the NMO group, patients with higher sCD27 concentrations exhibited worse disease disability in their CSF (p = 0.006). Moreover, the sCD27 concentrations had a significantly positive correlation with the level of CSF total protein (p = 0.030). Furthermore, the patients positive for AQP4-IgG (n = 26) seemed to have higher levels of sCD27 in their CSF (p = 0.069) than those negative for AQP4-IgG (n = 5). CONCLUSIONS: We revealed that the level of CSF sCD27 was elevated in NMOSD and correlated with NMOSD disease activity.

Late-onset neuromyelitis optica spectrum disorder in AQP4-seropositivepatients in a Chinese population.

BACKGROUND: Increasing rates of AQP4-seropositive neuromyelitis optica spectrum disorder (NMOSD) have been reported in late-onset patients (LONMOSD). However, the full range of clinical differences between early-onset and late-onset variants remain unclear. We describe the clinical features and outcomes of AQP4-seropositive LONMOSD patients in a Chinese population. METHODS: This was a retrospective analysis of medical records in a cohort study of AQP4-seropositive NMOSD patients with early-onset (≤49 years) and late-onset (≥50 years) variants between January 2006 and February 2014. Demographic, clinical, neuroimaging and cerebrospinal fluid (CSF) findings and prognosis data were analyzed. RESULTS: We identified thirty AQP4-seropositive LONMOSD patients (86.7 % women). The median age at onset was 57.5 years (range 50-70). There were similar onset frequencies between optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Longer interval between (first) ON and LETM (median 13 vs. 4 months; p < 0.05), time from first symptoms to diagnosis of NMO (median 17 vs. 7 months, p < 0.05), higher comorbidities (66.7 vs. 26.7 %; p < 0.05), and more hypertension (26.7 vs.3.3 %; p < 0.05) were prevalent. NMO-like lesions were less common (10.7 vs. 41.6 %; p < 0.05), while the rate of non-specific lesions tended to be higher (53.6 vs. 29 %; p = 0.067). These patients displayed more severe Expanded Disability Status Scale (EDSS) in nadir (median 6.75vs.5; p < 0.05). Attacks often resulted in EDSS 4 within a short period (median 8 vs. 13.5 months; p < 0.05). At last follow-up, the EDSS score was more severe in these patients (median 5.25 vs. 4; p < 0.05). No significant predictors were identified. CONCLUSIONS: This study provides an overview of the clinical and paraclinical features of AQP4-seropositive LONMOSD patients in China and demonstrates a number of distinct disease characteristics in early vs. late onset. Older patients are more susceptible to disability in short course. However, these patients do not always display NMO-like lesions in the brain. Initial LETM may not necessarily be predominant as the initial symptom, contrary to previous reports. The higher comorbidities may warrant a modified approach of treatment.

Association between neuromyelitis optica and tuberculosis in a Chinese population.

BACKGROUND: A number of reports have described the presence of tuberculosis (TB) in neuromyelitis optica (NMO) patients. However, a definite association between the two conditions has not been conclusively demonstrated. METHODS: To investigate the association between NMO and TB in a Chinese population, we performed a retrospective review of hospital records of NMO patients, control patients and tuberculosis meningitis (TBM) patients from January 1, 1995 to December 31, 2011. RESULTS: The frequency of preceding/simultaneous active pulmonary TB (PTB) was not significantly different between NMO patients (1.1%) and control groups (2.3% in myasthenia gravis, 1.1% in polymyositis or dermatomyositis, zero in idiopathic facial palsy and viral meningitis/meningoencephalitis). NMO cases differed from TBM cases in terms of demographics, course (recurrent or monophasic), cerebrospinal fluid analysis and magnetic resonance images. Two TBM patients shared partial clinical features with NMO (one of the TBM patients had a longitudinal extensive spinal cord lesion involving the holocord, and the other had optic neuritis before anti-tuberculosis treatment). NMO antibodies were only detected in NMO patients and not in TBM patients with myelitis or optic neuritis. CONCLUSIONS: We could not confirm previous suggestions of the association between PTB and NMO. Direct infection of the central nervous system by TB may mimic NMO in some respects, but whether NMO-like symptoms that develop during the course of TB should be considered and diagnosed as NMO is open to discussion.

Clinical and imaging features of patients with late-onset myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: There is an age-dependent change in the clinical phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the clinical features of late-onset MOGAD have not been well described. METHODS: Clinical data of 110 MOGAD patients, including 21 late-onset patients with onset age greater than or equal to 50 years old were retrospectively analyzed. RESULTS: Compared to pediatric- and younger adult-onset ones, late-onset MOGAD patients experienced milder disease onset (p < 0.001), more monophasic course (p < 0.001), fewer relapses (p = 0.007), less cerebrospinal fluid leukocytosis (p = 0.021), less longitudinally extensive transverse myelitis (onset p = 0.026, whole course p = 0.028), fewer lesions in basal ganglia (whole course p = 0.012), thalamus (whole course p = 0.040) and cerebellum (whole course p = 0.028). However, they had more cerebral symptoms (p = 0.021 onset and whole course), more lesions in white matter (onset p = 0.005, whole course p < 0.001) and periventricular area (onset p = 0.026), along with longer and delayed therapeutic intervention (p < 0.001). The main differences in clinical characteristics between late-onset patients with and without these brain involvements might be comorbidities. CONCLUSIONS: Late-onset MOGAD are more likely to experience delayed diagnosis. Brain involvement may be modulated by comorbidities of the elderly, which alter the clinical manifestations of late-onset MOGAD.

Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica.

BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune-mediated inflammatory diseases of the central nervous system. In the acute phase of these diseases, secondary ischemia due to inflammation-induced endothelial dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro-inflammatory protein and a novel biomarker of inflammatory vascular diseases. OBJECTIVE: We aimed to determine whether PTX3 levels are elevated in MS and NMO patients. METHODS: The concentrations of plasma PTX3 were measured using an enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer controls. RESULTS: During relapse, plasma PTX3 levels were higher in MS patients than in headache patients (p=0.003) and controls (p<0.001). Plasma PTX3 levels were also increased in NMO patients compared with CI patients (p=0.011), headache patients (p<0.001) and controls (p<0.001). CI patients showed elevated PTX3 levels compared with controls (p=0.008). MS and NMO patients showed a trend toward an increased disease disability with higher plasma PTX3 during relapse (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). CONCLUSION: Plasma PTX3 level is associated with inflammatory responses in MS and NMO.

Cerebrospinal fluid high-mobility group box protein 1 in neuromyelitis optica and multiple sclerosis.

BACKGROUND: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are two autoimmune inflammatory demyelinating diseases in the central nervous system. Interleukin (IL)-6 and IL-17 may play important roles in the pathogenesis of these diseases. High-mobility group box protein 1 (HMGB1) can activate the nuclear factor light chain enhancer of activated B cells and release cytokines such as IL-6 and IL-17. However, whether cerebrospinal fluid (CSF) HMGB1 levels were altered in NMO and MS patients is still unclear. OBJECTIVES: It was our aim to measure the CSF HMGB1 concentration in NMO patients and explore their relationship with IL-6, IL-17 and disease activity. METHODS: CSF HMGB1 was measured by enzyme-linked immunosorbent assay in NMO (n = 22) and MS (n = 18) patients as well as in controls (n = 14). RESULTS: CSF HMGB1 was notably higher in the NMO group compared with controls (p = 0.007). CSF HMGB1 positively correlated with IL-6 and IL-17 in NMO patients (IL-6, p = 0.034; IL-17, p < 0.001). CONCLUSIONS: In conclusion, our study suggests that CSF levels of HMGB1 are increased in patients with NMO and reflect the neuroinflammatory process.

IL2RA Allele Increases Risk of Neuromyelitis Optica in Southern Han Chinese.

BACKGROUND: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients. METHODS: Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing. RESULTS: The rs2104286(G) frequency in the IL2RA gene was significantly higher in NMO patients than in controls (p(uncorr)=0.013, p(corr)=0.026, OR:1.942, 95%CI:1.146-3.291). CONCLUSION: The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population.Les allèles IL2RA augmentent le risque de neuromyélite optique chez les Chinois Han du sud.

Evolution in anti-myelin oligodendrocyte glycoprotein antibody detection and its clinical significance: a narrative review.

Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressing on the surface of myelin sheaths and oligodendrocyte plasma membrane in the central nervous system of mammals, and it has a highly conserved nucleotide and amino acid structure between species. Evidence from animal research support that anti-MOG antibodies (MOG-Abs) are pathogenic antibodies rather than a bystander secondary to myelin destruction. Similarly, immunoglobulin-G against myelin oligodendrocyte glycoprotein (MOG-IgG) is considered a demyelinating disease-associated autoantibody in human beings. In clinical studies, several detection methods, including ELISA, immunoblot, radio immunoprecipitation assays and Cell-based assays (CBAs), have been applied in identifying MOG-Abs in idiopathic inflammatory demyelinating diseases (IIDDs) of human beings. CBAs method is recommended by many proposed diagnostic criterions for MOG-Abs-associated disorders (MOGAD). This method involves transfection of mammalian cells with MOG antigen, binding of MOG-Abs to MOG antigen, binding of secondary antibodies to MOG-Abs and quantification method. However, the reliability for CBAs systems of MOG-Abs detection can be influenced by numerous factors, such as length of MOG antigen, expression vectors, cell lines, secondary antibodies, and read-out systems. In addition, there are controversial results on the studies of IIDDs with MOG-IgG positive. Nowadays, more and more evidence suggests that patients positive for MOG-IgG share common features, but further clinical and laboratory researches are needed to clarify if MOGAD is an independent disease entity. In this review, we intend to summarize the detection methods of MOG-Abs and their sensitivity and specificity to MOGAD in human.

Cerebrospinal fluid α-synuclein levels are elevated in multiple sclerosis and neuromyelitis optica patients during replase.

The concept that the immune system plays a central role in the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) was indisputable. However, neurodegenerative pathological features including loss of axons and neurons were also found in the lesions of these diseases. α-Synuclein is one of the most abundant proteins in pre-synaptic terminals. Recently, many research show α-synuclein level in CSF may reflect the progression of synaptic dysfunction and neuronal apoptosis. Whether the levels of CSF α-synuclein are changed in MS and NMO patients remain unknown. In this study, CSF α-synuclein was measured by an enzyme-linked immunosorbent assay (ELISA) in MS (n = 18) patients, NMO (n = 22) patients, Parkinson's disease patients (n = 9), and the controls (n = 11). We found concentration of α-synuclein in MS and NMO patients were significantly higher than Parkinson's disease subgroup and the controls. Both MS and NMO revealed an increased disease disability with increased CSF α-synuclein. Thus, CSF α-synuclein may be reflect injure axons and neurons in inflammatory demyelinating diseases.

Cerebrospinal fluid BAFF and APRIL levels in neuromyelitis optica and multiple sclerosis patients during relapse.

BACKGROUND: BAFF (B-cell activating factor of the tumor necrosis factor family) and APRIL (a proliferation-inducing ligand) are two of the major survival factors for B cells. Many studies have shown that BAFF levels were elevated in MS patients. However, whether the levels of CSF BAFF/APRIL increased in NMO patients was still unclear. OBJECTIVE: To measure the CSF BAFF and APRIL concentration of in NMO patients, and explore their relationship with disease activity in NMO. METHODS: CSF BAFF and APRIL was measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n = 22), MS (n = 18) patients and controls (n = 14). RESULTS: Concentration of BAFF and APRIL in NMO patients were significantly higher than MS and controls. CSF BAFF and APRIL levels in controls were also lower than MS. Both NMO and MS revealed an increased disease disability with increased CSF BAFF. CSF APRIL was associated with EDSS scores in NMO, but not found in MS. CONCLUSIONS: BAFF/APRIL system considered important for aggressive B cells and T-cell responses, and may stimulates B cells and T cell activation in acute relapse of NMO and MS. In NMO patients, CSF BAFF and APRIL may be key factors of B cell immune response and reflect disease severity.