Human Metabotropic Glutamate Receptor 5 Antibodies Alter Receptor Levels and Behavior in Mice

Maudes, Estibaliz; Mannara, Francesco; García‐Serra, Anna; Radosevic, Marija; Mellado, Araceli; Serafim, Ana Beatriz; Planagumà, Jesús; Sabater, Lidia; Dalmau, Josep; Spatola, Marianna

doi:10.1002/ana.26362

Cited by 13 publications

(6 citation statements)

References 19 publications

(44 reference statements)

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“…These results were similar to the previous findings (7). A recent study has revealed that mGluR5 antibodies can reduce the level of mGluR5 in the hippocampus, causing memory loss and anxiety in mice, which was in agreement with the clinical phenotype of anti-mGluR5 encephalitis (6). Other common neurologic symptoms include sleep disturbances, seizures, decreased level of consciousness, and movement disorders, which is align with previous studies (4, 7-9).…”

supporting

confidence: 92%

“…Autoimmune encephalitis with mGluR5 antibodies was first reported in two patients with limbic encephalitis and Hodgkin's lymphoma (Ophelia syndrome) in 2011 (4). A recent study in an animal model has confirmed the pathogenicity of mGluR5 antibodies, which causes a reduction of mGluR5 clusters in neurons (6). However, as far as we know, since 2011, only 15 autoimmune encephalitis patients with mGluR5 antibodies from 8 studies have been reported worldwide, including three case reports from China (4,(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

et al. 2023

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BackgroundOnly 15 patients of autoimmune encephalitis with metabotropic glutamate receptor 5 (mGluR5) antibodies have been reported worldwide since 2011, mostly from western countries. Patients with different genetic backgrounds are necessary to further clarify the clinical phenotype and prognosis of this rare disease.ObjectiveWe initially describe a case series from China to confirm the previous findings, expand the clinical phenotype, and identify the prognostic factors of autoimmune encephalitis with mGluR5 antibodies.MethodsObservational data with follow-up were prospectively collected from autoimmune encephalitis patients with mGluR5 antibodies. Clinical information and outcomes on current and previously reported cases were combined and analyzed.ResultsWe identified five patients (median age 35 years); two were female. The main clinical manifestations were behavioral/personality changes (five of five, 100%) and cognitive disorders (four of five, 80%), accompanied with other neurologic symptoms. Hypoventilation occurred in two (40%) patients, which was life-threatening. One patient had meningoencephalitis, suggesting a new phenotype in anti-mGluR5 encephalitis. All patients received immunotherapy. At the last follow-up (median 18 months), two (40%) patients showed complete recovery, two (40%) patients showed partial recovery, and one (20%) patient died. One (20%) patient had multiple relapses. Together with the 15 previously reported cases, associated tumors occurred in seven of 12 (58%) Western patients vs. one of eight (13%) Chinese patients. Modified Rankin Scale (mRS) scores at the last follow-up (median 31 months) were available in 16 patients. Patients with bad outcomes (mRS > 2, n = 4) were more likely to have hypoventilation at onset and higher mRS scores at peak of the disease.ConclusionsIn patients with different genetic background, as Chinese, the clinical phenotype of anti-mGluR5 encephalitis is similar. Fewer paraneoplastic cases were observed in Chinese patients. Most patients showed good responses to immunotherapy and cancer treatment. The clinical outcomes were favorable in most patients.

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confidence: 92%

Section: Introductionmentioning

confidence: 99%

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

et al. 2023

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“…The prevailing pathogenic hypothesis of post‐HSE anti‐NMDAR encephalitis suggests that viral infection damages neurons and exposes NMDAR antigens located on the neuronal surface, initiating a series of autoimmune responses (Dalmau & Graus, 2018). Given that mGluR5s are widespread in the brain, a reduced density of mGluR5 clusters on the neuronal surface was noticed in anti‐mGluR5 encephalitis (Maudes et al., 2022), we speculate that the mechanism of post‐HSE anti‐mGluR5 encephalitis is similar to anti‐NMDAR encephalitis.…”

Section: Discussionmentioning

confidence: 61%

Anti‐metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review

Chen,

Ren,

Lin

et al. 2023

Brain and Behavior

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Objective: To describe the clinical and radiological characteristics of anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis. Methods:We reviewed the clinical data of five patients with anti-mGluR5 encephalitis, and performed a literature review. Results:The five cases included a 52-year-old man who developed a biphasic course of anti-mGluR5 encephalitis after herpes simplex encephalitis, a 22-year-old woman who showed bilateral basal ganglia lesions on brain magnetic resonance imaging (MRI), and a 36-year-old man with mixed aphasia and generalized tonic-clonic seizures, a 51-year-old man presented with personality changes, hallucinations, delusions, sleeping disorders and a 58-year-old man with short-term memory deficits and absence seizures.. There are 16 reported cases of anti-mGluR5 encephalitis worldwide. Of all 21 patients, with a median onset age of 35 years old, the main neurological symptoms were cognitive impairment (85.7%, 18/21), psychiatric or behavior problems (76.2%, 16/21), seizures (57.1%, 12/21), sleeping disorders (52.4%, 11/21), different degrees of decreased consciousness (42.9%, 9/21), and movement disorders (23.8%, 5/21). Brain MRI was normal in 11 of 21 patients. Lesions of the limbic lobes were presented in 5 patients, while involvement of other extralimbic regions was also reported. Seven of 21 (33.3%) cases were combined with tumors. Elevated white blood cell counts or specific oligoclonal IgG bands in the cerebrospinal fluid were found in 18 of 21 patients, with marked improvements observed after immunotherapy.Discussion: Patients with anti-mGluR5 encephalitis typically present with diffuse, rather than purely limbic, encephalitis. Anti-mGluR5 encephalitis can be triggered by herpes simplex encephalitis. The risk of a combined tumor may be reduced in anti-mGluR5 encephalitis patients.

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“…However, nothing was known about the pathological mechanisms of the autoantibodies until 2018, when it was found that patient mGluR5 autoantibodies, mainly of the IgG1 subclass, decreased the amount of mGluR5 clusters on rat hippocampal neurons [ 86 ]. In 2019, it was further reported that the patient’s autoantibodies caused anxiety and progressive memory loss in mice [ 165 ]. The two publications have been authored by the same group and none of the pathological mechanisms have been validated by an independent research group.…”

Section: Autoantibodies With Extracellular Targetsmentioning

confidence: 99%

Pathophysiological Effects of Autoantibodies in Autoimmune Encephalitides

Ryding,

Mikkelsen,

Nissen

et al. 2023

Cells

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The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis.

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Human Metabotropic Glutamate Receptor 5 Antibodies Alter Receptor Levels and Behavior in Mice

Cited by 13 publications

References 19 publications

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

Autoimmune encephalitis with mGluR5 antibodies: A case series from China and review of the literature

Anti‐metabotropic glutamate receptor 5 encephalitis: Five case reports and literature review

Pathophysiological Effects of Autoantibodies in Autoimmune Encephalitides

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