Patrick Joseph Waters

University of Oxford | OX · Nuffield Department of Clinical Neurosciences

Importance A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti–myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term d...

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that...

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, c...

Reported rates of Epstein–Barr virus (EBV) seropositivity in children meeting multiple sclerosis (MS) diagnostic criteria are considerably lower than those reported in adult‐onset MS, putting in question a requisite role for EBV in MS development. As prior work preceded recognition of myelin oligodendrocyte glycoprotein‐associated disease (MOGAD),...

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 prot...

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. Methods:...

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 MOGAD patients. Methods: A retrospe...

This case-control study investigates the positivity rates of the most prevalent neuroglial surface antibodies during the COVID-19 pandemic.

Serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG) are found in patients with acquired CNS demyelinating syndromes that are distinct from multiple sclerosis and aquaporin-4-seropositive neuromyelitis optica spectrum disorder. Based on an extensive literature review and a structured consensus process, we propose diagnostic c...

Autoantibody testing is the mainstay in confirming the diagnosis of autoimmune myasthenia gravis (MG). However, in approximately 15% of patients, antibody testing in clinical routine remains negative (seronegative MG). This study aimed at assessing the prevalence of “clustered” AChR- and MuSK- and LRP4- autoantibodies using a live cell-based assay...

Background We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. Methods A...

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...

Introduction Leucine-rich glioma-inactivated 1 (LGI1) is one of the most common surface neuronal autoantigens associated with autoimmune limbic encephalitis (LE) in humans, with hallmarks of personality change, amnesia and seizures. Recently, these autoantibodies were described in domestic cats with LE, likewise with a distinctive phenotype of beha...

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. In a subset of patients with MG, muscle-specific tyrosine kinase (MuSK) autoantibodies are present. MuSK MG patients respond well to CD20-mediated B cell depletion therapy (BCDT); most achieve complete stable remission. However, relapse often occur...

Objective Patients with myasthenia gravis without acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibodies detected by radioimmunoprecipitation assays (RIAs) are classified as seronegative myasthenia gravis (SNMG). Live cell-based assays (l-CBAs) can detect additional antibodies to clustered AChR, MuSK and low-density lipoprotein r...

Significance By studying paired blood and deep cervical lymph node samples from patients with neuromyelitis optica spectrum disorders, our data provide evidence for a germinal center–based generation of aquaporin-4 antibodies. Frequent serum aquaporin-4 immunoglobulin Ms (IgMs) and shifts in IgG subclasses were observed alongside preferential synth...

Background Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is now recognized as distinct from multiple sclerosis (MS). Objective To evaluate the importance of considering myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin-G (IgG) serology when applying MS diagnostic criteria in children. Methods Within a prospective...

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. Metho...

Background: The importance of autoimmune encephalitis and its overlap with infectious encephalitides are not well investigated in South-East Asia. Methods: We report autoantibody testing, using antigen-specific live cell-based assays, in a series of 134 patients (cerebrospinal fluid and sera) and 55 blood donor controls (sera), undergoing lumbar...

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...

Background: We studied the prevalence of neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in Indigenous populations of Australia and New Zealand with the aim of assessing potential differences. Methods: Cases of possible NMOSD and MS were collected from Australia and New Zealand. Clinical details, MR imaging, and serolo...

Patients with autoimmune encephalitides, especially those with antibodies to the N-methyl-d-aspartate receptor (NMDAR), often present with prominent psychosis and respond well to immunotherapies. Although most patients progress to develop various neurological symptoms, it has been hypothesised that a subgroup of patients with first-episode psychosi...

Background : Neuromyelitis optica spectrum disorder (NMOSD) is associated with significant morbidity and mortality. Several therapies have been recommended for NMOSD and more recently clinical trials have demonstrated efficacy for three monoclonal antibody therapies. We present a retrospective observational study of treatment response in NMOSD. Me...

Objective To identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD). Setting Patients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions. Participants...

Importance: The recognition of magnetic resonance imaging (MRI) features associated with distinct causes of myelitis in children is essential to guide investigations and support diagnostic categorization. Objective: To determine the clinical and MRI features and outcomes associated with spinal cord involvement in pediatric myelin oligodendrocyte...

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are inflammatory diseases of the CNS. Overlap in the clinical and MRI features of NMOSD and MS means that distinguishing these conditions can be difficult. With the aim of evaluating the diagnostic utility of MRI features in distinguishing NMOSD from MS, we have conducted a...

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cum...

Pain is a recognized association with LGI1-/ CASPR2-antibodies. Of 147 patients, pain was experienced by 17/33 (52%) CASPR2- versus 20/108 (19%) LGI1-antibody patients (p=0.0005), and identified as neuropathic in 89% versus 58% of these, respectively. Typically, normal nerve conduction studies and reduced intraepidermal nerve fibre densities were o...

Objective To analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases. Methods Retrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating dise...

The autoimmune encephalitis (AE) syndromes have been characterised by the detection of autoantibodies in serum and/or cerebrospinal fluid which target the extracellular domains of specific neuroglial antigens. The clinical syndromes have phenotypes which are often highly characteristic of their associated antigen-specific autoantibody. For example,...

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associ...

Objective Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody–associated disorders (MOGAD), we performed detailed characterization of an Australasian...

Background The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (...

Anti‐myelin oligodendrocyte glycoprotein immunoglobulin G (MOG‐IgG) antibodies are associated clinically with either a monophasic or relapsing disease course. We investigated the frequency and clinical importance of acquired asymptomatic brain magnetic resonance imaging (MRI) lesions in a prospective incident cohort of 74 MOG‐IgG positive children...

A 39-year-old lady with relapsing myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease developed coryzal symptoms, malaise, sweating, and postural dizziness. Six days later she presented with painful progressive right visual loss consistent with optic neuritis. COVID-19 was confirmed by nasopharyngeal swab and MOG-IgG serologic...

Objective To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this clinical setting. Methods Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy. Results 10.5% (23/219)...

Myelin oligodendrocyte glycoprotein (MOG) is a unique CNS-specific mammalian protein that is expressed on the surface of compact myelin and oligodendrocyte cell bodies. MOG is an accessible target for autoantibodies, associated with immune-mediated demyelination in the central nervous system. The identification of MOG reactive immunoglobulin G anti...

Introduction: The majority of patients with myasthenia gravis (MG) initially present with ocular symptoms but it is difficult to predict which cases will remain as ocular MG (OMG) or will progress to generalized MG. Here, we evaluated the serological profile of Japanese OMG and its relationship with clinical features. Methods: Seventy-three pati...

This study aimed to characterise both neuronal autoantibodies and levels of IFNα, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). CSF and plasma from 35 SLE patients (15 with NPSLE) showed no antibodies against natively-expressed NMDA receptors, or the surface of live hippocampal neurons. By comparison to con...

Autoantibodies to leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein like-2 (CASPR2) are associated with clinically distinctive syndromes that are highly immunotherapy responsive, such as limbic encephalitis, faciobrachial dystonic seizures, Morvan’s syndrome and neuromyotonia. These autoantibodies target surface-exposed doma...

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) show overlap in their clinical features. We performed an analysis of relapses with the aim of determining differences between the two conditions. Cases of NMOSD and age- and sex-matched MS controls were collected from across Australia and New Zealand. Demographic and clinic...

Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal prepa...

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic...

Background The bone health in neuromyelitis optica spectrum disorder with aquaporin-4 immunoglobulin G antibodies (NMOSD-AQP4) have not been fully evaluated. To evaluate the prevalence of fractures and bone loss in patients with NMOSD-AQP4 compared to healthy controls and patients with multiple sclerosis (MS) and to identify the risk factors associ...

Objective: To compare the reproducibility of 11 antibody assays for immunoglobulin (Ig) G and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG and MOG-IgM) from 5 international centers. Methods: The following samples were analyzed: MOG-IgG clearly positive sera (n = 39), MOG-IgG low positive sera (n = 39), borderline negative sera (n...

Background: Given that the spectrum of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated disease is yet to be fully defined, development of sensitive and highly specific assays to identify MOG-IgG is crucial to precisely define the clinical phenotypes, disease courses and prognosis to describe the full spectrum of MOG-IgG a...

Objective: Drug-resistant seizures are common in patients with Leucine-rich, glioma-inactivated-1 (LGI1) and contactin-associated-protein-like-2 (CASPR2)-IgG associated encephalitis. We performed the first randomized double-blind placebo-controlled trial to evaluate efficacy of intravenous immunoglobulin (IVIG) in reducing seizure frequency. Meth...

Objectives: To compare the reproducibility of 11 antibody assays for IgG and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG, MOG-IgM) from five international centers. Methods: The following samples were analyzed: MOG-IgG clearly positive sera (n=39), MOG-IgG low positive sera (n=39), borderline negative sera (n=13), clearly negative se...

Glycine-receptor(GlyR) antibodies are well defined in progressive encephalomyelitis with rigidity and myoclonus (PERM), and are associated with a limited spectrum of immunotherapy-responsive syndromes. Whilst paradigms of autoantibody pathogenicity have been proposed, the trigger and propagation of GlyR antibodies remains unclear. We herein describ...

Objective: To determine whether unsupervised principal component analysis (PCA) of comprehensive clinico-radiologic data can identify phenotypic subgroups within antibody-negative patients with overlapping features of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs), and to validate the phenotypic classifications using...

We have compared five different assays for antibodies to aquaporin-4 in 181 cases of suspected Neuromyelitis optica spectrum disorders (NMOSD) and 253 controls to assess their relative utility. As part of a clinically-based survey of NMOSD in Australia and New Zealand, cases of suspected NMOSD were referred from 23 centers. Clinical details and mag...

Importance Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. Objective To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospe...

Glycine receptor (GlyR) antibodies are well described in a narrow spectrum of clinically-related immunotherapy-responsive syndromes of which progressive encephalomyelitis with rigidity and myoclonus (PERM) is the most common. Whilst molecular paradigms of autoantibody-mediated pathogenicity have been characterised, triggers of the conditions and me...

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by muscle weakness and caused by pathogenic autoantibodies that bind to membrane proteins at the neuromuscular junction. Most patients have autoantibodies against the acetylcholine receptor (AChR), but a subset of patients have autoantibodies against muscle-specific tyrosine kina...

Objectives To re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and neuromyelitis optica (NMO). Methods We re-screened 103/114 patients with available serum on live cell-bas...

Objective We sought to validate methods for detection and confirmation of GABA A receptor (R)-IgG and clinically characterize seropositive cases.Methods Archived serum and CSF specimens (185 total) suspected to harbor GABA A R-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious fo...

The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) (n = 194, HD n = 64), 2) type 1 diabetes (T1D) (n = 200, HD n =...