Publications by authors named "Patrick Waters"

Many forms of autoimmune encephalitis are mediated by neuronal cell-surface directed autoantibodies. The co-occurrence of four neuronal cell-surface antibodies in a single patient is exceptionally rare. We report a patient who had a severe encephalitis associated with antibodies to NMDA, Glycine, GABA and GABA receptors.

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Background: Antibodies against the N-methyl-D-aspartate receptor (NMDAR) have been described in the serum of people with schizophrenia spectrum disorders (schizophrenia). However, the prevalence and clinical relevance of these antibodies in schizophrenia is unclear. This knowledge gap includes the possibility of such antibodies being associated with a distinct clinical profile, which in turn might warrant a distinct treatment approach.

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Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.

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  • A study investigated the impact of the timing of treatment for the first acute attack of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) on long-term relapse risk and conversion to MOG-IgG seronegative status.
  • Conducted in South Korea, the research involved a cohort of 240 adults diagnosed with MOGAD, focusing on their treatment timing categorized as early, intermediate, or late.
  • Results indicated that 45.8% of patients experienced relapses and 25% converted to seronegative MOG-IgG, highlighting the potential significance of timely treatment in managing MOGAD.
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Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases.

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An adaptive immune response in less than 1% of people who develop cancer produces antibodies against neuronal proteins. These antibodies can be associated with paraneoplastic syndromes, and their accurate detection should instigate a search for a specific cancer. Over the years, multiple systems, from indirect immunofluorescence to live cell-based assays, have been developed to identify these antibodies.

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  • Epstein-Barr virus (EBV) seropositivity rates in children with multiple sclerosis (MS) are notably lower compared to adults, raising questions about EBV's necessity in MS development.
  • A study analyzed 251 children with demyelination and found that when accounting for MOGAD (myelin oligodendrocyte glycoprotein-associated disease), over 90% of MS children had evidence of EBV infection.
  • The results support EBV's significant role in the MS spectrum while highlighting different biological mechanisms between MS and MOGAD.
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Intrathecal synthesis of central nervous system (CNS)-reactive autoantibodies is observed across patients with autoimmune encephalitis (AE), who show multiple residual neurobehavioral deficits and relapses despite immunotherapies. We leveraged two common forms of AE, mediated by leucine-rich glioma inactivated-1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, as human models to comprehensively reconstruct and profile cerebrospinal fluid (CSF) B cell receptor (BCR) characteristics. We hypothesized that the resultant observations would both inform the observed therapeutic gap and determine the contribution of intrathecal maturation to pathogenic B cell lineages.

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Background And Objectives: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation.

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Background: The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients' clinical characteristics.

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Objective: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer-term relapse risk is unknown. Here, we investigate whether early relapses increase longer-term relapse risk in patients with MOGAD.

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  • The study investigates how pediatric MOG antibody-associated disease (MOGAD) affects brain growth in children compared to healthy peers and those with MS or monophasic demyelination, highlighting the possible impact on brain maturation.* -
  • Researchers included children diagnosed with MOGAD, MS, or monophasic demyelination from a longitudinal study and used brain MRI scans to analyze regional brain volumes against normative data from healthy children.* -
  • Findings revealed that children with MOGAD show significant delays in expected brain growth, particularly in areas like the thalamus and caudate, indicating a deviation from typical brain development patterns.*
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Background And Objectives: Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.

Methods: We identified patients with acetylcholine receptor antibody-positive (AChR) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses.

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  • MOG antibodies are linked to specific types of CNS demyelinating syndromes that differ from multiple sclerosis and aquaporin-4-seropositive neuromyelitis optica spectrum disorder.* -
  • A proposed set of diagnostic criteria for MOG antibody-associated disease (MOGAD) emphasizes that the presence of MOG-IgG is crucial and typically associates with conditions like acute disseminated encephalomyelitis, optic neuritis, or transverse myelitis.* -
  • Validating these criteria could enhance the diagnosis of MOGAD, which is important for understanding long-term clinical outcomes and for refining clinical trial criteria, though not all multiple sclerosis patients need to be tested for MOG-IgG.*
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  • * It involved a retrospective analysis of 160 patients, ultimately narrowing down to 89 AChR Ab-negative MG patients, finding that 24.7% tested positive for anti-MuSK antibodies via ELISA, showing high agreement with other testing methods.
  • * The findings suggest that while CBA is more sensitive for detecting anti-MuSK antibodies, ELISA may still have valuable diagnostic applications, especially when distinguishing between MuSK MG and conditions with similar symptoms, like motor neuron disease.
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Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. A small subset of patients (<10%) with MG, have autoantibodies targeting muscle-specific tyrosine kinase (MuSK). MuSK MG patients respond well to CD20-mediated B cell depletion therapy (BCDT); most achieve complete stable remission.

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A range of studies suggest that a proportion of psychosis may have an autoimmune basis, but this has not translated through into clinical practice-there is no biochemical test able to accurately identify psychosis resulting from an underlying inflammatory cause. Such a test would be an important step towards identifying who might require different treatments and have the potential to improve outcomes for patients. To identify novel subgroups within patients with acute psychosis we measured the serum nuclear magnetic resonance (NMR) metabolite profiles of 75 patients who had identified antibodies (anti-glycine receptor [GlyR], voltage-gated potassium channel [VGKC], Contactin-associated protein-like 2 [CASPR2], leucine-rich glioma inactivated 1 [LGI1], N-methyl-D-aspartate receptor [NMDAR] antibody) and 70 antibody negative patients matched for age, gender, and ethnicity.

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Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population.

Methods: Ninety-nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary-care hospitals in Sri Lanka were studied.

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  • Patients with seronegative myasthenia gravis (SNMG) often lack detectable antibodies, but live cell-based assays (l-CBAs) can reveal additional antibodies to AChR, MuSK, and LRP4.
  • In a study of 82 SNMG patients, 19.5% had antibodies to clustered AChR and 8.5% had MuSK antibodies; a combined assay effectively detected these antibodies more efficiently.
  • Patients with these antibodies generally had milder disease and better outcomes when treated soon after diagnosis compared to those with traditional RIA-detected antibodies.
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Autoantibodies against the extracellular domain of the N-methyl-d-aspartate receptor (NMDAR) NR1 subunit cause a severe and common form of encephalitis. To better understand their generation, we aimed to characterize and identify human germinal centres actively participating in NMDAR-specific autoimmunization by sampling patient blood, CSF, ovarian teratoma tissue and, directly from the putative site of human CNS lymphatic drainage, cervical lymph nodes. From serum, both NR1-IgA and NR1-IgM were detected more frequently in NMDAR-antibody encephalitis patients versus controls (both P < 0.

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