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Rare variants and HLA haplotypes associated in Serbian patients with Neuromyelitis Optica Spectrum Disorders

ABSTRACT: Rare variants and HLA haplotypes associated in Serbian patients with Neuromyelitis Optica Spectrum Disorders

PROVIDER: PRJNA879241 | ENA |

REPOSITORIES: ENA

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Rare variants and HLA haplotypes associated in Serbian patients with Neuromyelitis Optica Spectrum Disorders

Project description:Rare variants and HLA haplotypes associated in Serbian patients with Neuromyelitis Optica Spectrum Disorders

| PRJNA879242 | ENA

Rare variants and HLA haplotypes associated in patients with neuromyelitis optica spectrum disorders.

Project description:Neuromyelitis optica spectrum disorders (NMOSD) are rare, debilitating autoimmune diseases of the central nervous system. Many NMOSD patients have antibodies to Aquaporin-4 (AQP4). Prior studies show associations of NMOSD with individual Human Leukocyte Antigen (HLA) alleles and with mutations in the complement pathway and potassium channels. HLA allele associations with NMOSD are inconsistent between populations, suggesting complex relationships between the identified alleles and risk of disease. We used a retrospective case-control approach to identify contributing genetic variants in patients who met the diagnostic criteria for NMOSD and their unaffected family members. Potentially deleterious variants identified in NMOSD patients were compared to members of their families who do not have the disease and to existing databases of human genetic variation. HLA sequences from patients from Belgrade, Serbia, were compared to the frequency of HLA haplotypes in the general population in Belgrade. We analyzed exome sequencing on 40 NMOSD patients and identified rare inherited variants in the complement pathway and potassium channel genes. Haplotype analysis further detected two haplotypes, HLA-A*01, B*08, DRB1*03 and HLA-A*01, B*08, C*07, DRB1*03, DQB1*02, which were more prevalent in NMOSD patients than in unaffected individuals. In silico modeling indicates that HLA molecules within these haplotypes are predicted to bind AQP4 at several sites, potentially contributing to the development of autoimmunity. Our results point to possible autoimmune and neurodegenerative mechanisms that cause NMOSD, and can be used to investigate potential NMOSD drug targets.

| S-EPMC9578444 | biostudies-literature

ATP mediates neuropathic pain of neuromyelitis optica spectrum disorder via microglial activation

Project description:Intractable neuropathic pain is recognized as a common symptom of neuromyelitis optica spectrum disorder (NMOSD). However, the underlying mechanism of NMOSD pain remains to be elucidated. Here, we established NMOSD pain model by injecting anti-AQP4 recombinant autoantibodies (AQP4-Ab) generated from NMOSD patient’s plasmablasts into rat spinal cords and confirmed the development of mechanical allodynia. AQP4-Ab mediated extracellular ATP release from astrocytes and pharmacological inhibition of ATP receptor reversed mechanical allodynia in NMOSD pain model. Furthermore, transcriptome analysis revealed microglia activation and IL-1β elevation in NMOSD spinal cord. Inhibition of microglia activation and neutralization of IL-1β also attenuated neuropathic pain in NMOSD rat model. In addition, the human CSF ATP concentration was significantly higher in the acute and remission phase of NMOSD than in multiple sclerosis and other neurological disorder patients. These findings indicate ATP, microglial activation and IL-1β secretion orchestrates the pathogenesis of NMOSD neuropathic pain.

2021-08-24 | GSE150598 | GEO

ATP mediates neuropathic pain of neuromyelitis optica spectrum disorder via microglial activation

Project description:ATP mediates neuropathic pain of neuromyelitis optica spectrum disorder via microglial activation

| PRJNA632887 | ENA

A multiomic approach to reveal gastrointestinal toxicity mechanisms associated with mycophenolate mofetil in neuromyelitis optica spectrum disorders

Project description:Mycophenolate mofetil (MMF) has been widely prescribed for neuromyelitis optica spectrum disorders (NMOSD) although some patients experience severe gastrointestinal (GI) side effects following MMF administration. Our study investigated the potential mechanisms of this toxicity in NMOSD patients. We constructed MMF-induced colitis mouse model and produced a multi-omic dataset in which microbiome and metabolome analysis from the mouse GI tract to decipher the mechanisms of MMF GI toxicity. Further, 17 female NMOSD patients treated with MMF were prospectively enrolled and grouped according to the diarrhea symptom as non-diarrhea NMOSD group (NM) and diarrhea NMOSD group (DNM) as well as healthy controls (HC, 12 female). The gut microbiota was analyzed using 16S rRNA sequencing of stool samples. In the mouse model, we found that vancomycin administration drastically altered the colon content metabolomes and microbiomes and prevented MMF-induced body weight loss, cecal and colon tissue injury. Bacteroidetes and Firmicutes converted phenyl-beta-D-glucuronide (MPAG) to mycophenolic acid (MPA) that could result in damaged intestinal tissue. We also demonstrated that the alpha diversity in the DNM group was increased and this was accompanied by increased Firmicutes and Proteobacteria abundance. Collectively, these results reveal that alterations of the gut microbiome and metabolome contribute to MMF-induced colitis. Modifying of the gut microbiome and metabolome may alleviate MMF-induced GI toxicity in NMOSD patients.

2024-06-18 | MTBLS4392 | MetaboLights

Differential serum proteomics of neuromyelitis spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)

Project description:Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are two types of autoimmune-mediated central nervous system (CNS) inflammatory demyelinating diseases that have similar clinical manifestations but with different pathogenesis and prognosis. Here we reported on a serum differential proteomic analysis of the patients with the two diseases. Sera of 25 Aquaporin-4 (AQP4)-IgG+ NMOSD patients, 16 MOGAD patients and 8 healthy people were submitted to shotgun analysis using nano-LC-MS/MS. Totally 584 non-redundant proteins were identified, among which 340 proteins were detected in at least three samples per group. Statistical analysis revealed 40 proteins have significant difference in at least one pair-comparison (fold change >=1.2 or <=0.83 and multi-sample test ANOVA-q <0.05). Further, 38 proteins were detected only in the patient groups and not in the healthy control group. Bioinformatic analysis on these 78 proteins revealed that disturbance on immune system, hemostasis processes and carbohydrate metabolism occurred in both diseases, but with different mechanisms. We believe this work could provide useful information to improve the understanding of the mechanisms of NMOSD and MOGAD and suggest potential diagnostic markers and treatment targets.

2024-12-25 | PXD059225 |

Neuromyelitis optica spectrum disorders.

Project description:Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Long segments of spinal cord inflammation (myelitis), severe optic neuritis, and/or bouts of intractable vomiting and hiccoughs (area postrema syndrome) are classic presentations of the disease and may alert the clinician to the diagnosis. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Relapses are treated aggressively to prevent residual disability with high-dose steroids and often plasma exchange. Relapse prevention is crucial and achieved with long-term immunosuppression. In this article we review the pathogenesis, clinical features, diagnosis and management of NMOSD.

| S-EPMC6454358 | biostudies-literature

Transcriptome signature of Neuromyelitis spectrum disorder under steroid tapering

Project description:Transcriptome signature of Neuromyelitis spectrum disorder under steroid tapering

| PRJNA1132253 | ENA

Transcriptome Sequencing of Optic Nerve in a Rat Model of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis (NMOSD-ON)

Project description:Transcriptome Sequencing of Optic Nerve in a Rat Model of Neuromyelitis Optica Spectrum Disorder-Related Optic Neuritis (NMOSD-ON)

| PRJNA1241179 | ENA

human gut metagenome

Project description:Intestinal Microbiota of Neuromyelitis Optica Raw sequence reads

| PRJNA422961 | ENA