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 |
REPOSITORIES: biostudies-literature
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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
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.
| S-EPMC8553315 | 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
Project description:BackgroundHelicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear.ObjectiveTo evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection.MethodsIn all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain).ResultFrequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD & MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p- 0.0001). Seropositive patients with MOGAD- MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+.ConclusionsIn developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence - a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases.
| S-EPMC10250711 | biostudies-literature
Project description:BackgroundPain is a frequent symptom in aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG-pos. NMOSD). Data on pain in myelin-oligodendrocyte-glycoprotein-immunoglobulin-G autoimmunity with a clinical NMOSD phenotype (MOG-IgG-pos. NMOSD) are scarce.ObjectiveThe objective of this paper is to investigate pain in MOG-IgG-pos. NMOSD, AQP4-IgG-pos. NMOSD and NMOSD without AQP4/MOG-IgG detection (AQP4/MOG-IgG-neg. NMOSD).MethodsForty-nine MOG-IgG-pos. (n = 14), AQP4-IgG-pos. (n = 29) and AQP4/MOG-IgG-neg. (n = 6) NMOSD patients were included in this cross-sectional baseline analysis from an ongoing observational study. We identified spinal cord lesions on magnetic resonance imaging, assessed pain by the painDETECT and McGill Pain questionnaires, quality of life by Short Form Health Survey, and depression by Beck Depression Inventory.ResultsTwelve MOG-IgG-pos. NMOSD patients (86%), 24 AQP4-IgG-pos. NMOSD patients (83%), and all AQP4/MOG-IgG-neg. NMOSD patients (100%) suffered from pain. MOG-IgG-pos. NMOSD patients had mostly neuropathic pain and headache; AQP4-IgG-pos. and AQP4/MOG-IgG-neg. NMOSD patients had mostly neuropathic pain. A history of myelitis was less frequent in MOG-IgG-pos. NMOSD than in AQP4-IgG-pos. NMOSD patients. Pain influenced quality of life in all patients. Thirty-six percent of patients with pain received pain medication; none of them were free of pain.ConclusionsPain is a frequent symptom of patients with MOG-IgG-pos. NMOSD and is as important as in AQP4-IgG-pos. and AQP4/MOG-IgG-neg. NMOSD. Despite its impact on quality of life, pain is insufficiently alleviated by medication.
| S-EPMC6117869 | biostudies-literature
Project description:Aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (AQP4-IgG seropositive NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) are inflammatory demyelinating disorders distinct from each other and from multiple sclerosis (MS).While anti-CD20 treatments can be used to treat MS and AQP4-IgG seropositive NMOSD, some MS medications are ineffective or could exacerbate AQP4-IgG seropositive NMOSD including beta-interferons, natalizumab, and fingolimod. AQP4-IgG seropositive NMOSD has a relapsing course in most cases, and preventative maintenance treatments should be started after the initial attack. Rituximab, eculizumab, inebilizumab, and satralizumab all have class 1 evidence for use in AQP4-IgG seropositive NMOSD, and the latter three have been approved by the US Food and Drug Administration (FDA). MOGAD is much more likely to be monophasic than AQP4-IgG seropositive NMOSD, and preventative therapy is usually reserved for those who have had a disease relapse. There is a lack of any class 1 evidence for MOGAD preventative treatment. Observational benefit has been suggested from oral immunosuppressants, intravenous immunoglobulin (IVIg), rituximab, and tocilizumab. Randomized placebo-controlled trials are urgently needed in this area.
| S-EPMC9294102 | biostudies-literature
Project description:BackgroundThe flare of immune-mediated disease following coronavirus disease of 2019 (COVID-19) vaccination is a rare adverse event following immunization. De novo, as well as relapsing IgA nephropathy (IgAN) cases, have been reported following either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccination. To our knowledge, the majority of IgAN relapses did not result in severe acute kidney injury (AKI) and resolved spontaneously.Case presentationThis is a case of a 54-year-old female with a previous diagnosis of IgAN who developed IgAN relapse following the second dose of Moderna vaccine. Gross hematuria developed 2 days after vaccination, which was accompanied by significant AKI. Kidney biopsy showed mild tubular atrophy and IgA staining in mesangium without crescent formation. Significant improvement in serum creatinine (Cr) was observed on day 10 after initiating prednisone. Cr came back to normal within 3 months after initiating corticosteroid.ConclusionCOVID-19 vaccination is associated with a flare of IgAN that may cause significant AKI. Steroid therapy is associated with recovery. IgAN flare after COVID-19 vaccination should be closely monitored to elucidate any adverse effect associated with the novel vaccine.
| S-EPMC8988530 | biostudies-literature
Project description:Objectives Several studies suggested that coronavirus disease 2019 (COVID-19) vaccination may lead to uveitis, a vision-threatening condition often associated with a variety of autoimmune or autoinflammatory diseases. This study aims to explore factors that influence the risk of uveitis relapse after COVID-19 vaccination to guide the prevention of disease. Methods Uveitis relapse was evidenced by worsening activity of intraocular inflammation (e.g. anterior chamber cells, vitreous haze) as defined by the Standardization of Uveitis Nomenclature Working Group. Time to uveitis relapse since the administration of each dose of COVID-19 vaccine was compared across participants with modifiable variables. Results The primary analysis included 438 non-COVID-19 participants with 857 doses of COVID-19 vaccine administered in total. The median age was 41 years (interquartile range, 30 to 51), and 57.3% were female. A total of 39 episodes of uveitis relapse events occurred in 34 patients after the receipt of a dose of COVID-19 vaccine within 30 days. The median time to relapse after vaccination was 5 days (interquartile range, 1 to 14). Concomitant use of systemic glucocorticoids at the time of vaccination was independently associated with a decrease in risk of relapse after vaccination (HR, 0.23 [95% CI, 0.07–0.74]; P value = 0.014). There was a trend in attenuating the risk of relapse with increasing prednisone dose from none to less than 20 mg per day and then to 20 mg per day or greater (P value for trend = 0.029). Conclusions Concomitant treatment with systemic glucocorticoids for uveitis at the time of COVID-19 vaccination was associated with a dose-dependent lower risk of uveitis relapse after vaccination.
| S-EPMC9531657 | biostudies-literature