Absence of Autoantibodies Against Neuronal Surface Antigens in Sera of Patients With Psychotic Disorders

Hoffmann, Carolin; Zong, Shenghua; Mané-Damas, Marina; Molenaar, Peter; Losen, Mario; Titulaer, Maarten J.; Martínez‐Martínez, Pilar

doi:10.1001/jamapsychiatry.2019.3679

Cited by 9 publications

(13 citation statements)

References 6 publications

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“…This has caused considerable interest in investigating a potential role for neuronal antibodies in the pathogenesis of psychiatric syndromes. Various casecontrol studies have produced conflicting results, but a systematic review and meta-analysis found that serum NMDAR antibodies were three times as common in patients with schizophrenia, schizoaffective disorder, bipolar affective disorder or major depressive disorder compared to controls 117,118 . This finding was supported by a more recent large case-control study indicating that serum NMDAR antibodies were more prevalent in patients with first episode psychosis than in the healthy controls, although this was not the case for the other antibodies tested; LGI1, GABA A R and VGKC-complex 119 .…”

Section: Psychiatric Disordersmentioning

confidence: 99%

Cognitive impact of neuronal antibodies: encephalitis and beyond

et al. 2020

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Cognitive dysfunction is a common feature of autoimmune encephalitis. Pathogenic neuronal surface antibodies are thought to mediate distinct profiles of cognitive impairment in both the acute and chronic phases of encephalitis. In this review, we describe the cognitive impairment associated with each antibody-mediated syndrome and, using evidence from imaging and animal studies, examine how the nature of the impairment relates to the underlying neuroimmunological and receptor-based mechanisms. Neuronal surface antibodies, particularly serum NMDA receptor antibodies, are also found outside of encephalitis although the clinical significance of this has yet to be fully determined. We discuss evidence highlighting their prevalence, and association with cognitive outcomes, in a number of common disorders including cancer and schizophrenia. We consider mechanisms, including blood-brain barrier dysfunction, which could determine the impact of these antibodies outside encephalitis and account for much of the clinical heterogeneity observed.

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Section: Psychiatric Disordersmentioning

confidence: 99%

Cognitive impact of neuronal antibodies: encephalitis and beyond

et al. 2020

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“…IHC studies: 2.2% of the samples were found positive with 11 novel patterns Plasma samples from 2231 individuals were initially tested by IHC on rat brain tissue, as described 27 . Overall, 106 (4.8%) samples had scores of 1 or higher, of which 56 (2.4%) samples had score 1 (borderline), 42 (1.8%) had score 2 (weak positive), and 8 (0.4%) had score 3 (strong positive) ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…To test if autoantibodies directly target neuronal surface proteins, rat hippocampal neuronal staining was performed as described previously 27,30 , with small modifications. In brief, neurons were incubated with patients' sera, followed by incubation with anti-human IgG fluorescentlabeled secondary antibody (supplementary Table 1) for 1 h and mounted with mounting medium containing DAPI; all the steps were performed at room temperature.…”

Section: Staining On Live Neuronsmentioning

confidence: 99%

“…In this study, we investigated autoantibodies binding to brain tissue, with a focus on NSAbs in the plasma from a large cohort of patients with depression and/or anxiety as well as from control individuals. We followed a tandem procedure, combining different methods including IHC on rat brain, staining on live-cultured rat hippocampal neurons and CBA as reported 27 .…”

Section: Introductionmentioning

confidence: 99%

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Novel neuronal surface autoantibodies in plasma of patients with depression and anxiety

et al. 2020

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Neuronal surface autoantibodies (NSAbs) against various antigens cause autoimmune encephalitis. Some of these antigens are also involved in the pathology of depression and anxiety. To study whether NSAbs are more common in plasma of individuals with depression and anxiety than in controls, and to investigate if NSAbs correlate with disease status, plasma samples of 819 individuals with a current diagnosis of depression and/or anxiety, 920 in remission and 492 individuals without these disorders were included in this study. Samples were tested by a combination of immunohistochemistry (IHC), staining on live rat hippocampus neurons and cell-based assay (CBA). By IHC, 50 (2.2%) samples showed immunoreactivity to rat brain tissue, with no significant differences between the aforementioned groups (22/819 vs 18/920 vs 11/492, P > 0.99). In addition, eight IHC positive samples were positive for NSAbs on live neurons (7/819 vs 0/920 vs 1/492, P = 0.006). The IHC-staining patterns of these eight samples were atypical for autoimmune encephalitis and accordingly, they tested negative for known NSAbs by CBA. No obvious difference in the clinical characteristics between individuals with or without NSAbs was observed. In conclusion, novel NSAbs were rare but predominately found in patients with current anxiety or depression indicating they might affect mental health in a small group of patients.

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“…Rat brain sections and primary cell cultures from rat embryo hippocampus were used to detect IgG autoantibodies to neuronal antigens ( 3 ). A strong immunoreactivity of serum antibodies to the middle region of the dentate gyrus and the molecular layer of the cerebellum was identified, with a titer of 1:1,600.…”

Section: Antibody and Antigen Characterizationmentioning

confidence: 99%

Unidentified Neuronal Surface IgG Autoantibodies in a Case of Hashimoto's Encephalopathy

et al. 2020

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is an encephalitis of presumed autoimmune origin characterized by the presence of autoantibodies against thyroid proteins. We present a case of a young patient with pre-existing Hashimoto's thyroiditis and progressive cognitive complaints, absence-like episodes, and sporadic bilateral epileptiform frontal and frontotemporal activity. No abnormalities were observed during the neurological examination and on MRI. Antibodies to thyroid peroxidase (TPO) were elevated and remained positive while the symptoms were present. Levothyroxine and methylprednisolone did not ameliorate the complaints. Subsequent treatment with high-dose intravenous immunoglobulins (IVIG) led to improved cognitive functions and to the disappearance of the absence-like-episodes. Patient's serum, but not CSF, gave a characteristic IgG-specific hippocampal pattern in rat brain immunohistochemistry; this immunoreactivity was maintained after specific and complete depletion of TPO antibodies. Serum IgG bound to primary neurons in cell culture, likely targeting a yet unidentified neuronal surface antigen. The clinical response to IVIG suggests but does not prove, that the circulating novel autoantibodies may induce the encephalopathy. It would be of interest to investigate more patients with Hashimoto's encephalopathy for the presence of neuronal surface autoantibodies, to define their role in the disease and their target antigen(s).

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Absence of Autoantibodies Against Neuronal Surface Antigens in Sera of Patients With Psychotic Disorders

Cited by 9 publications

References 6 publications

Cognitive impact of neuronal antibodies: encephalitis and beyond

Cognitive impact of neuronal antibodies: encephalitis and beyond

Novel neuronal surface autoantibodies in plasma of patients with depression and anxiety

Unidentified Neuronal Surface IgG Autoantibodies in a Case of Hashimoto's Encephalopathy

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