Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.
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ABSTRACT:
SUBMITTER: Dinoto A
PROVIDER: S-EPMC8607690 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
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Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.
Dinoto Alessandro A Sechi Elia E Ferrari Sergio S Gajofatto Alberto A Orlandi Riccardo R Solla Paolo P Maccabeo Alessandra A Maniscalco Giorgia Teresa GT Andreone Vincenzo V Sartori Arianna A Manganotti Paolo P Rasia Sarah S Capra Ruggero R Mancinelli Chiara Rosa CR Mariotto Sara S
Multiple sclerosis and related disorders 20211122
Post-vaccination disease relapses have been reported in patients with MOGAD and AQP4-IgG+NMOSD. In this retrospective multicenter Italian study we assessed the frequency of relapses after SARS-CoV-2 vaccination. We included 56 cases: MOGAD, 30; AQP4-IgG+NMOSD, 26. Vaccines received were BNT162b2-Pfizer-BioNTech in 42 patients and mRNA-1273-Moderna in 14 patients. Six patients had a history of SARS-CoV-2 infection; two of them experienced a post-infection disease relapse (MOGAD). The frequency of ...[more]
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Project description:ObjectiveAquaporin-4-antibody-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder (MOGAD) are relapsing neuroinflammatory diseases, frequently leading to chronic pain. In both diseases, the spinal cord (SC) is often affected by myelitis attacks. We hypothesized that regional SC volumes differ between AQP4-IgG + NMOSD and MOGAD and that pain intensity is associated with lower SC volumes. To evaluate changes in the SC white matter (WM), gray matter (GM), and pain intensity in patients with recent relapses (myelitis or optic neuritis), we further profiled phenotypes in a case series with longitudinal imaging and clinical data.MethodsCross-sectional data from 36 participants were analyzed in this retrospective study, including 20 AQP4-IgG + NMOSD and 16 MOGAD patients. Pain assessment was performed in all patients by the Brief Pain Inventory and painDETECT questionnaires. Segmentation of SC WM, GM, cervical cord volumes (combined volume of WM + GM) was performed at the C2/C3 cervical level. WM% and GM% were calculated using the cervical cord volume as a whole per patient. The presence of pain, pain severity, and clinical disability was evaluated and tested for associations with SC segmentations. Additionally, longitudinal data were deeply profiled in a case series of four patients with attacks between two MRI visits within one year.ResultsIn AQP4-IgG + NMOSD, cervical cord volume was associated with mean pain severity within 24 h (β = -0.62, p = 0.009) and with daily life pain interference (β = -0.56, p = 0.010). Cross-sectional analysis showed no statistically significant SC volume differences between AQP4-IgG + NMOSD and MOGAD. However, in AQP4-IgG + NMOSD, SC WM% tended to be lower with increasing time from the last attack (β = -0.41, p = 0.096). This tendency was not observed in MOGAD. Our case series including two AQP4-IgG + NMOSD patients revealed SC GM% increased by roughly 2% with either a myelitis or optic neuritis attack between visits. Meanwhile, GM% decreased by 1-2% in two MOGAD patients with a myelitis attack between MRI visits.ConclusionIn AQP4-IgG + NMOSD, lower cervical cord volume was associated with increased pain. Furthermore, cord GM changes were detected between MRI visits in patients with disease-related attacks in both groups. Regional SC MRI measures are pertinent for monitoring disease-related cord pathology in AQP4-IgG + NMOSD and MOGAD.
| S-EPMC10853470 | biostudies-literature
Project description:BackgroundThere is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands.ObjectiveTo investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients.MethodsA cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images.ResultsIn total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003).ConclusionThe pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.
| S-EPMC10306980 | biostudies-literature
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Project description:IntroductionNeuromyelitis optica spectrum disorder (NMOSD; also known as Devic syndrome) is a clinical syndrome of central nervous system characterized by immune mediated attacks of acute optic neuritis and myelitis. Paraneoplastic neurological syndrome is a group of nervous system disorders resulting from the remote immune effects of malignant neoplasm. NMOSD occurs mostly in young people, and tumor is not a common cause, especially recurrent tumor.MethodsWe reported a case of a 59-year-old man who developed anti-aquaporin-4 IgG positive longitudinally extensive myelitis. We also summarized and analyzed previously reported cases of paraneoplastic NMOSD.ResultsAmong these 43 patients, 88.4% patients are female. The largest number of patients is between 60 and 69 years old. Breast cancer and lung cancer are the most common types. The most common lesions were located in the cervicothoracic region with patchy gadolinium enhancement. The existing treatment can only delay rather than stop the progress of the disease.ConclusionIt is necessary to perform tumor screening in patients with NMOSD, especially patients over 50 years.
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Project description:ObjectivesData on peripheral blood mononuclear cells (PBMCs) characteristics of aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking. In this study, we describe the whole PBMCs landscape of the above diseases using cytometry by time-of-flight mass spectrometry (CyTOF).MethodsThe immune cell populations were phenotyped and clustered using CyTOF isolated from 27 AQP4-IgG seropositive NMOSD, 11 MOGAD patients, and 15 healthy individuals. RNA sequencing was employed to identify critical genes. Fluorescence cytometry and qPCR analysis were applied to further validate the algorithm-based results that were obtained.ResultsWe identified an increased population of CD11b+ mononuclear phagocytes (MNPs) in patients with high expression of CCR2, whose abundance may correlate with brain inflammatory infiltration. Using fluorescence cytometry, we confirmed the CCR2+ monocyte subsets in a second cohort of patients. Moreover, there was a wavering of B, CD4+ T, and NKT cells between AQP4-IgG seropositive NMOSD and MOGAD.ConclusionsOur findings describe the whole landscape of PBMCs in two similar demyelinated diseases and suggest that, besides MNPs, T, NK and B, cells were all involved in the pathogenesis. The identified cell population may be used as a predictor for monitoring disease development or treatment responses.
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Project description:PurposeTo emphasize physio-pathological, clinical and prognosis differences between conditions causing serious and sometimes very similar clinical manifestations: anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies related diseases, and seronegative NMOSD (neuromyelitis optica spectrum disorders).MethodsBased on Wingerchuk et al. (Neurology 85:177-189, 2015) criteria for NMOSD and on those more recently proposed by Jarius et al. (J Neuroinflammation 15:134, 2018) for MOGAD (MOG associated disorders), we retrospectively surveyed 10 AQP4-NMOSD, 8 MOGAD and 2 seronegative NMOSD, followed at the specialized neuroimmunology unit of the CHU Liège.ResultsFemale predominance was only observed in AQP4 group. Age at onset was 37.8 and 27.7 years old for AQP4-NMOSD and MOGAD respectively. In both groups, the first clinical event most often consisted of optic neuritis (ON), followed by isolated myelitis. Fifteen of our 20 patients encountered a relapsing course with 90% relapses in AQP4-NMOSD, 62.5% in MOGAD and 50% in seronegative group, and a mean period between first and second clinical event of 7.1 and 4.8 months for AQP4-NMOSD and MOGAD, respectively. In total we counted 54 ON, with more ON per patient in MOGAD. MOG-associated ON mainly affected the anterior part of the optic nerve with a papilledema in 79.2% of cases. Despite a fairly good visual outcome after MOG-associated ON, retinal nerve fibre layer (RNFL) thickness decreased, suggesting a fragility of the optic nerve toward further attacks.ConclusionAs observed in larger cohorts, our MOGAD and AQP4-NMOSD cases differ by clinical and prognostic features. A better understanding of these diseases should encourage prompt biological screening and hasten proper diagnosis and treatment.
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Project description:BackgroundThe effect of smoking on the resolution of magnetic resonance imaging (MRI) lesions in patients with neuromyelitis optica spectrum disorders with aquaporin-4 positive antibody (NMOSD-AQP4) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has not been studied before.ObjectiveWe aimed to determine the effect of smoking on lesion resolution in MRI and assess its correlation with clinical recovery after a relapse.MethodsWe conducted a cohort study including NMOSD-AQP4 and MOGAD patients with acute and follow-up MRI scans. We collected demographic, clinical, imaging and smoking data. Logistic regression models were fitted to predict the effect of smoking on lesion resolution and to assess whether clinical recovery was associated with MRI lesion resolution.ResultsA total of 105 patients were included (57 with NMOSD-AQP4 and 48 with MOGAD). Current and past smoking was associated with a higher risk of persistent lesions in NMOSD-AQP4 and MOGAD (risk ratio (RR) = 3.4, 95% confidence interval (CI) = 2.5-4.7, p < 0.001). Additionally, the presence of lesion resolution was associated with better clinical recovery (RR = 1.9, 95% CI = 1.7-2.2, p < 0.001).ConclusionSmoking is associated with worse MRI lesion resolution in patients with NMOSD-AQP4 and MOGAD, and lesion resolution correlates with clinical recovery. Our findings suggest a detrimental effect of smoking in inflammatory central nervous system (CNS) diseases.
| S-EPMC10503243 | biostudies-literature
Project description:BackgroundThe SARS-CoV-2 Omicron variant appears to cause milder infections, however, its capacity for immune evasion and high transmissibility despite vaccination remains a concern, particularly in immunosuppressed patients. Herein, we investigate the incidence and risk factors for COVID-19 infection in vaccinated adult patients with Multiple Sclerosis (MS), Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD), and Myelin Oligodendrocyte Glycoprotein-antibody associated disease (MOGAD) during the Omicron subvariant BA.1/2 wave in Singapore.MethodsThis was a prospective observational study conducted at the National Neuroscience Institute, Singapore. Only patients who had at least two doses of mRNA vaccines were included. Data on demographics, disease characteristics, COVID-19 infections and vaccinations, and immunotherapies were collected. SARS-CoV-2 neutralising antibodies were measured at various time points after vaccination.ResultsTwo hundred and one patients were included; 47 had COVID-19 infection during the study period. Multivariable logistic regression revealed that receipt of a third SARS-CoV-2 mRNA vaccination (V3) was protective against COVID-19 infection. No particular immunotherapy group increased the risk of infection, however, Cox proportional-hazards regression showed that patients on anti-CD20s and sphingosine-1-phosphate modulators (S1PRMs) had a shorter time to infection after V3, compared to those on other immunotherapies or not on immunotherapy.ConclusionsThe Omicron subvariant BA.1/2 is highly infectious in patients with central nervous system inflammatory diseases; three doses of mRNA vaccination improved protection. However, treatment with anti-CD20s and S1PRMs predisposed patients to earlier infection. Future studies are required to determine the protective efficacy of newer bivalent vaccines that target the Omicron (sub)variant, especially in immunocompromised patients.
| S-EPMC10080502 | biostudies-literature
Project description:ObjectiveNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated disorder with aquaporin 4-immunoglobulin G (AQP4-IgG) in most settings. Soluble programmed death-1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) play key roles in immunomodulation. We aim to assess the association of sPD-1 and sPD-L1 with cytokines and their clinical significance in AQP4-IgG (+) NMOSD.MethodWe measured plasma sPD-1, sPD-L1, and 10 cytokines levels of 66 AQP4-IgG (+) NMOSD patients, including 40 patients in attack (attack-NMOSD) and 26 patients in remission (remission-NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP-X platform, respectively. We also performed >2 years (median) of follow-up after testing and analyzed the relationship between the detection index and current and future clinical parameters.ResultPlasma sPD-1 level discriminated attack-NMOSD from remission-NMOSD (AUC = 0.692, p = 0.009). sPD-1 and sPD-L1 levels positively correlated with IL-6 (rsPD-1 = 0.313; rsPD-L1 = 0.508), IFN-γ (rsPD-1 = 0.331; rsPD-L1 = 0.456), and TNF-α (rsPD-1 = 0.451; rsPD-L1 = 0.531) expression, as well as clinical indicators, including the EDSS score (rsPD-1 = 0.331; rsPD-L1 = 0.402), number of attacks (rsPD-1 = 0.431) and segments of spinal cord involvement (rsPD-1 = 0.462; rsPD-L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD-1/sPD-L1 ratio in attack-NMOSD (p = 0.022; Exp(B) = 1.589).InterpretationPlasma sPD-1 and sPD-L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4-IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment.
| S-EPMC10863926 | biostudies-literature
Project description:BackgroundPrior studies have suggested that subclinical retinal abnormalities may be present in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD), in the absence of a clinical history of optic neuritis (ON).ObjectiveOur aim was to compare retinal layer thicknesses at the fovea and surrounding macula between AQP4-IgG+ NMOSD eyes without a history of ON (AQP4-nonON) and healthy controls (HC).MethodsIn this single-center cross-sectional study, 83 AQP4-nonON and 154 HC eyes were studied with spectral-domain optical coherence tomography (OCT).ResultsTotal foveal thickness did not differ between AQP4-nonON and HC eyes. AQP4-nonON eyes exhibited lower outer nuclear layer (ONL) and inner photoreceptor segment (IS) thickness at the fovea (ONL: -4.01 ± 2.03 μm, p = 0.049; IS: -0.32 ± 0.14 μm, p = 0.029) and surrounding macula (ONL: -1.98 ± 0.95 μm, p = 0.037; IS: -0.16 ± 0.07 μm, p = 0.023), compared to HC. Macular retinal nerve fiber layer (RNFL: -1.34 ± 0.51 μm, p = 0.009) and ganglion cell + inner plexiform layer (GCIPL: -2.44 ± 0.93 μm, p = 0.009) thicknesses were also lower in AQP4-nonON compared to HC eyes. Results were similar in sensitivity analyses restricted to AQP4-IgG+ patients who had never experienced ON in either eye.ConclusionsAQP4-nonON eyes exhibit evidence of subclinical retinal ganglion cell neuronal and axonal loss, as well as structural evidence of photoreceptor layer involvement. These findings support that subclinical anterior visual pathway involvement may occur in AQP4-IgG+ NMOSD.
| S-EPMC8200372 | biostudies-literature