Analysis of CH25H in multiple sclerosis and neuromyelitis optica.
Ontology highlight
ABSTRACT:
SUBMITTER: Forwell AL
PROVIDER: S-EPMC5092160 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Analysis of CH25H in multiple sclerosis and neuromyelitis optica.
Forwell Amanda L AL Bernales Cecily Q CQ Ross Jay P JP Yee Irene M IM Encarnacion Mary M Lee Joshua D JD Sadovnick A Dessa AD Traboulsee Anthony L AL Vilariño-Güell Carles C
Journal of neuroimmunology 20151231
Oxysterols produced by CH25H during cholesterol metabolism have been shown to play an important role in the immune response. In this study we report the genetic characterization of CH25H in patients diagnosed with multiples sclerosis (MS) or neuromyelitis optica (NMO), for the identification of genetic variants affecting disease susceptibility and course. Exome analysis in 212 MS and 14 NMO patients identified a rare CH25H p.Q17H mutation in two NMO patients of Asian ancestry. In addition, assoc ...[more]
Similar Datasets
Project description:Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.
| S-EPMC4425816 | biostudies-other
Project description:Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR, multivariate statistics, one-way ANOVA, and univariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid cycle, and glycolysis. Metabolites altered in urine from MS patients were shown to be related to known pathogenic processes relevant to MS, including alterations in energy and fatty acid metabolism, mitochondrial activity, and the gut microbiota.
| S-EPMC4772670 | biostudies-literature
Project description:ObjectiveTo assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)-positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS).MethodsWe screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20).ResultsDifferential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well-discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD.ConclusionsWhile AQP4-Ab-positive and -negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS.
| S-EPMC4747481 | biostudies-literature
Project description:Vitamin D deficiency is prevalent in all ages regardless of climate or geographical location and evidence is emerging that the incidence of autoimmune diseases is increasing worldwide. Women make up a large proportion of autoimmune disease diagnoses, underscoring the importance of fully elucidating the complex synergistic relationships between estrogens and vitamin D. Vitamin D receptor-activating drugs appear to enhance remyelination in patients diagnosed with multiple sclerosis (MS) and other demyelinating diseases such as neuromyelitis optica (NMO). This review is intended to update health practitioners about the potential role of vitamin D deficiency demyelination and to motivate future research on dietary recommendations for vitamin D in preventing and treating demyel1nating diseases.
| S-EPMC7187724 | biostudies-literature
Project description:BackgroundMultiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.Methods/principal findingsSamples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.ConclusionsThese findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.
| S-EPMC3749992 | biostudies-literature
Project description:IntroductionCognitive impairment is a common feature of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, there is a lack of population-based study of dementia risk in these disorders. In the present study, the risk of dementia in MS and NMOSD patients in Republic of Korea was estimated.MethodsData analyzed in this study were obtained from the Korean National Health Insurance Service (KNHIS) database between January 2010 and December 2017. The study included 1,347 MS patients and 1,460 NMOSD patients ≥40 years of age who had not been diagnosed with dementia within 1 year prior to the index date. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, or dyslipidemia.ResultsIn MS and NMOSD patients, the risk of developing any dementia [adjusted hazard ratio (aHR) = 2.34; 95% confidence interval (CI) = 1.84-2.96 and aHR = 2.19; 95% CI = 1.61-3.00, respectively], Alzheimer's disease [AD; aHR = 2.23; 95% confidence interval (CI) = 1.70-2.91 and aHR = 1.99; 95% CI = 1.38-2.88, respectively], and vascular dementia (aHR = 3.75; 95% CI = 1.91-7.35 and aHR = 3.21; 95% CI = 1.47-7.02, respectively) was higher compared with the matched controls. NMOSD patients had a lower risk of any dementia and AD compared with MS patients after adjusting for age, sex, income, hypertension, diabetes, and dyslipidemia (aHR = 0.67 and 0.62).ConclusionThe risk of dementia increased in MS and NMOSD patients and dementia risk was higher in MS than in NMOSD.
| S-EPMC10309000 | biostudies-literature
Project description:ObjectiveWe tested whether brain gray matter (GM) imaging measures can differentiate between multiple sclerosis (MS) and neuromyelitis optica (NMO) using random-forest classification.MethodsNinety participants (25 patients with MS, 30 patients with NMO, and 35 healthy controls [HCs]) were studied in Tehran, Iran, and 54 (24 patients with MS, 20 patients with NMO, and 10 HCs) in Padua, Italy. Participants underwent brain T1 and T2/fluid-attenuated inversion recovery MRI. Volume, thickness, and surface of 50 cortical GM regions and volumes of the deep GM nuclei were calculated and used to construct 3 random-forest models to classify patients as either NMO or MS, and separate each patient group from HCs. Clinical diagnosis was the gold standard against which the accuracy was calculated.ResultsThe classifier distinguished patients with MS, who showed greater atrophy especially in deep GM, from those with NMO with an average accuracy of 74% (sensitivity/specificity: 77/72; p < 0.01). When we used thalamic volume (the most discriminating GM measure) together with the white matter lesion volume, the accuracy of the classification of MS vs NMO was 80%. The classifications of MS vs HCs and NMO vs HCs achieved higher accuracies (92% and 88%).ConclusionsGM imaging biomarkers, automatically obtained from clinical scans, can be used to distinguish NMO from MS, even in a 2-center setting, and may facilitate the differential diagnosis in clinical practice.Classification of evidenceThis study provides Class II evidence that GM imaging biomarkers can distinguish patients with NMO from those with MS.
| S-EPMC5177679 | biostudies-literature
Project description:BackgroundNeuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients.MethodsTwelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP).Principal findingsEuropean ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population.ConclusionsOur findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.
| S-EPMC3604018 | biostudies-literature
Project description:Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.
| S-EPMC4575169 | biostudies-literature
Project description:Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a cross-sectional analysis of imaging data and developed predictive models to distinguish the two conditions. NMOSD and MS MRI lesions were identified and defined through a literature search. Aquaporin-4 (AQP4) antibody positive NMOSD cases and age- and sex-matched MS cases were collected. MRI of orbits, brain and spine were reported by at least two blinded reviewers. MRI brain or spine was available for 166/168 (99%) of cases. Longitudinally extensive (OR = 203), "bright spotty" (OR = 93.8), whole (axial; OR = 57.8) or gadolinium (Gd) enhancing (OR = 28.6) spinal cord lesions, bilateral (OR = 31.3) or Gd-enhancing (OR = 15.4) optic nerve lesions, and nucleus tractus solitarius (OR = 19.2), periaqueductal (OR = 16.8) or hypothalamic (OR = 7.2) brain lesions were associated with NMOSD. Ovoid (OR = 0.029), Dawson's fingers (OR = 0.031), pyramidal corpus callosum (OR = 0.058), periventricular (OR = 0.136), temporal lobe (OR = 0.137) and T1 black holes (OR = 0.154) brain lesions were associated with MS. A score-based algorithm and a decision tree determined by machine learning accurately predicted more than 85% of both diagnoses using first available imaging alone. We have confirmed NMOSD and MS specific MRI features and combined these in predictive models that can accurately identify more than 85% of cases as either AQP4 seropositive NMOSD or MS.
| S-EPMC8458658 | biostudies-literature