Optimization of an Anti-NMDA Receptor Autoantibody Diagnostic Bioassay

Chiu, Nan Chang; Lin, Yu–Chen; Tzang, Ruu Fen; Li, Ying Syuan; Lin, Hui Ju; Das, Subir Kumar; Chen, Caleb G.; Chen, Chiao Chicy; Hsu, Kate

doi:10.3389/fneur.2018.00661

Cited by 5 publications

(7 citation statements)

References 27 publications

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“…It is well-known that the antibody of AE can remain unknown in up to 40-50% of cases [6,7]. Moreover, the false-negative result of anti-NMDA IgG antibodies, including CSF with commercial laboratory kit testing, has led to new laboratory techniques to improve the sensitivity of antibody testing [8,9].…”

Section: Discussionmentioning

confidence: 99%

Atypical Brain MRI Findings in a Child With Delayed Diagnosis of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Jan¹,

Anilkumar²

2021

Cureus

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Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is the most common cause of autoimmune encephalitis in children with a wide spectrum of clinical presentation and MRI findings. A high index of suspicion is required to avoid a delay in treatment and long-term morbidity. We present a healthy two-yearold male who developed fever and viral prodrome symptoms that rapidly progressed to acute encephalopathy, status epilepticus, quadriparesis, and abnormal movements. Brain MRI showed symmetric involvement of bilateral insula, posterior part of basal ganglia, and thalami. The patient survived the acute phase with supportive therapy but ended up with a devastating neurologic sequela, including developmental delay, inability to communicate, dysphagia, quadriparesis, and cortical visual impairment. Anti-N-methyl-D-aspartate (anti-NMDA) immunoglobulin G (IgG) antibodies were negative in serum and cerebrospinal fluid (CSF). The patient underwent an extensive inflammatory, infectious, metabolic, and genetic workup, including a whole-exome sequence (WES) and mitochondrial panel, which was unremarkable. CSF studies were unremarkable. Repeated anti-NMDA IgG antibodies were positive in serum a year after the presentation. This presentation highlights the crucial role of early immunotherapy in suspected autoimmune encephalitis (AE) cases, even at a young age, to prevent devastating neurologic outcomes. Moreover, clinicians should not rely on antibody results to treat a suspected case of AE due to possible falsenegative test results, and the majority of AE cases remain without known antibodies.

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Section: Discussionmentioning

confidence: 99%

Atypical Brain MRI Findings in a Child With Delayed Diagnosis of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Jan¹,

Anilkumar²

2021

Cureus

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“…The only symptom was partial seizures in the right limb [11]. False positiveness of anti-NMDAR antibody in both serum and CSF was also reported in Lyme disease [12], False positiveness in serum has been found in multiple sclerosis [13], Creutzfeldt-Jakob disease [14], and schizophrenia [15].Therefore, besides autoantibodies detection, careful clinical observation is also warranted. False negative result is also possible.…”

Section: Discussionmentioning

confidence: 99%

Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report

et al. 2020

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Background Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a severe autoimmune encephalitis mediated by anti-NMDA receptor antibodies. Brain MRI manifestations vary and are non-specific. If there are any lesions, they tend to be diffusely or multifocally distributed. Solitary lesion is relatively rare. Case presentation We report a 16-year-old girl who initially presented with focal seizures but developed severe psychiatric and extrapyramidal symptoms later on. Brain MRI revealed a solitary juxtacortical demyelinating lesion in the left frontal lobe. No enhancement was noted. Electroencephalogram captured epileptiform discharges in the same region. NMDAR IgGs were tested positive in the serum and cerebrospinal fluid. Corticosteroid and intravenous IgG were administered and the patient completely recovered. Brain MRI revealed a fainter lesion in the left frontal lobe. Conclusion In very rare instances, anti-NMDA receptor encephalitis can present with a solitary brain lesion. A full panel of antibodies for autoimmune encephalitis is the key leading to the diagnosis.

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“…Nan-Chang Chiu and his colleges found that replacing reporter fluorophore fluorescein isothiocyanate in the commercial kits with Alexa Fluor 488 could obtain better detection result, especially in samples with low titers (18) because the fluorescence from Alexa Fluor 488 was brighter and more stable (55,56). A more sophisticated optic/imaging device is recommended because it allows even weak signals to be displayed from samples with low titers.…”

Section: Optimization Of Detection Assays In Practicementioning

confidence: 99%

“…Some anti-NMDAR encephalitis patients could be misdiagnosed as mentally ill and missed early effective immunosuppressive therapy if they showed isolated psychiatric episodes in the early days. However, once these misdiagnosed patients received the individualized immunotherapy (first-line immunotherapy including corticosteroids, intravenous immunoglobulins or plasma exchange; or second-line immunotherapy such as rituximab or cyclophosphamide, or both, or long-term immunotherapy (mycophenolate mofetil or azathioprine >1 year), their symptoms could be gradually cured (18). Thus, improving the sensitivity and specificity of autoantibody diagnostic bioassay in NMDAR antibodies is meaningful.…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies detection in anti-N-methyl-D-aspartate receptor encephalitis

Li¹,

Wang²

2023

Ann Transl Med

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Autoimmune encephalitis (AE) covers a group of neurological diseases caused by autoantibodies.AE is severe but treatable. It has attracted more and more attention currently. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common AE characterized by specific autoantibody mainly against NMDAR subunit 1. Cell-based assays (CBA) on human embryonic kidney 293 (HEK293) cells and immunohistochemistry (IHC) on rat brain tissue have been widely used to detect antibody in patients with AE. However, few studies focused on the overview of these assays detecting autoantibodies in AE. Here we reviewed the detection assays in AE and compared the sensitivity and specificity of CBA and IHC. It's found that IHC got a higher positive rate than CBA in both serum and CSF when screening potential AE, while CBA was more specific. Besides, more positive samples were found in CSF than in serum by either IHC or CBA. Hence, both serum and CSF should be sent to detect antibodies by two assays to avoid misdiagnosis. CSF antibody titers were believed more clinically relevant. When positive results were shown in IHC but negative in CBA, other kinds of antibodies associated AE instead of anti-NMDAR encephalitis should be taken into account. Further studies should pay attention to serum testing for diagnosis or assessment of the disease, as CSF testing is invasive and not always available.

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Optimization of an Anti-NMDA Receptor Autoantibody Diagnostic Bioassay

Cited by 5 publications

References 27 publications

Atypical Brain MRI Findings in a Child With Delayed Diagnosis of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Atypical Brain MRI Findings in a Child With Delayed Diagnosis of Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Solitary juxtacortical lesion associated with anti-N-methyl-D-aspartate receptor encephalitis: a case report

Autoantibodies detection in anti-N-methyl-D-aspartate receptor encephalitis

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