Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 3, 2025

Background The advent of biologics has significantly transformed treatment strategies for neuromyelitis optica spectrum disorder (NMOSD). However, there are no biomarkers that predict relapses associated with steroid tapering; therefore, it is critical to identify potential indicators disease activity. In this study, we collected peripheral blood mononuclear cells (PBMCs) from NMOSD patients during tapering and performed bulk RNA sequencing analyze changes in immune dynamics caused by reduction. Methods PBMCs were at 3–5 timepoints 10 our hospital (including one relapse case), was performed. All positive anti-AQP4 antibodies had history biologic use. Results relapsed patient, gene groups decreased expression observed predominantly monocytes, upregulation anti-inflammatory pathways such as IL-10, while the upregulated genes related interferon signaling. Moreover, after tapering, non-relapsed patients, increased enriched inflammatory pathways, represented signaling, IL-10 glucocorticoid receptors. Weighted co-expression network analysis identified modules correlated dosage, inversely dosage marked signature pathway. Conclusion This study transcriptome signatures could lead identification clinically relevant activity biomarkers, further highlights pivotal role signaling NMOSD.

Язык: Английский

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Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8169 - 8169

Опубликована: Июль 26, 2024

Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between human and aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that humanization of AQP4 ECDs would make model lesions closer to NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated genome-editing technology, AQP4-specific monoclonal antibody (mAb) or six IgGs introduced intraperitoneally into hAQP4 wild-type Lewis (WT) after immunization with myelin basic protein complete Freund’s adjuvant. Human mAb induced astrocyte loss specifically in rats. The also NMOSD-like tissue-destructive loss, demyelination, axonal swelling, complement deposition, marked neutrophil macrophage/microglia infiltration rats; however, difference lesion size infiltrating cells was not significant WT bound both rat M23, suggesting their binding shared region ECDs. Anti-AQP4 titers positively correlated infiltration. Considering vary sites affinities some them may bind AQP4, our is expected reproduce pathology more accurately than

Язык: Английский

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Neuromyelitis optica spectrum disorder. Clinical case

INTERNATIONAL NEUROLOGICAL JOURNAL, Год журнала: 2024, Номер 20(5), С. 243 - 249

Опубликована: Сен. 29, 2024

Background. Neuromyelitis optica spectrum disorder (NMOSD) has been masked under other diagnoses for many years. Modern diagnostic criteria expand diagnosis possibilities, but they need approbation in real clinical practice. The purpose was through the analysis of a case and literature search to analyze algorithm making neuromyelitis based on new guideline “Diagnosis treatment disorders” developed 2023 Ukraine, identify marker signs that exclude alternative diagnoses, effectiveness patient dynamics. Materials methods. We used bibliosemantic method, as well methods systematic comparative analysis. presented results our own experience conducted dynamic optica. Results. Over past six years, 23 patients diagnosed with were treated at neurological department Lviv Regional Clinical Hospital: 1 2018, 5 2019, 3 2020, 6 2021, 8 2022. examined 52-year-old who sought medical help Department Neurology Danylo Halytskyi National Medical University 2023. analyzed patient’s path dynamics changes magnetic resonance imaging from considering current which included single term NMOSD. presence even one main manifestations, combination AQP4-IgG, gives grounds carried out differential pathologies. Based this, we identified multiple sclerosis, acute disseminated encephalomyelitis, infectious myelitis, diseases. Diagnostic aspects NMOSD options considered. An out. Conclusions. Ukrainian disorder, is international consensus criteria, improves standardization approach can be effectively In myelitis without optic neuritis, AQP4-IgG careful pathologies play key role diagnosing.

Язык: Английский

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Introductory Chapter: The New Era in Neuro-Ophthalmology – Challenges and Changes

IntechOpen eBooks, Год журнала: 2024, Номер unknown

Опубликована: Окт. 16, 2024

Язык: Английский

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Loss of Roquin-1 enhances CXCR5+PD-1+Tfh cell differentiation by interfere AMPK function to enhance glycolysis in Neuromyelitis Optica

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

Background Aquaporin-4 immunoglobulin G antibody (AQP4-IgG) product by B cells is essential in Neuromyelitis optica (NMO). However, some patients with immunosuppressive drugs persistently high AQP4-IgG titers, possibly owing to Follicular helper T (Tfh) can assist production. Roquin-1 has been linked the regulation of immune balance and plays an important role peripheral homeostasis cells. whether target Tfh differentiation NMO mechanism remain unclear. Hence, this study, we aim explore relationship between clinical characteristic NMO, AMPK regulates CXCR5 + PD-1 aggravate progression. Methods We enrolled 71 Clinical characteristics, MRI lesion counts spinal cord or brain, Expanded Disability Status Scale (EDSS) scores, expression levels, proportion were recorded analyzed each group using cell flow assay other studies. Then, validate ability, knockout overexpression along differentiation. Results In acute phase, mRNA was reduced, while remission it increased compared healthy controls. The higher than controls, there a negative correlation proportions expression. negatively correlated EDSS score positive percentage lesions. found that could affect function ratio during differentiation, promoted glycolysis-related proteins influencing interaction mTOR, improved secretion ability Conclusions Our study elucidated effect on corresponding protective autoimmunity, possible causes imbalance mechanisms, thus aiming provide novel insights into pathogenesis.

Язык: Английский

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Loss of Roquin-1 Enhances CXCR5+PD-1+ Tfh Cell Differentiation by Interfering with Ampkfunction to Enhance Glycolysis in AQP4-IgG–Positive Neuromyelitis Optica Spectrum Disorders

Опубликована: Янв. 1, 2024

Язык: Английский

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