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Case Reports
. 2026 Feb 10;273(2):134.
doi: 10.1007/s00415-026-13657-9.

Neuronal antibody targeting metabotropic glutamate receptor 8 in five cases and its pathogenicity

Pei-Hao Lin #  1 , Shi-Feng Zhang #  1 , Hai-Yan Yao #  1 , Wen-Dong Lai  1 , Shi-Yu He  1 , Shi-Chun Li  1 , Hui-Lu Li  2 , Zhan-Hang Wang  3 , Dong-Fang Cao  1 , Jie Yang  1 , Li Huang  1 , Ting Li  1 , Cong Gao  1 , Cong-Cong Fu  4 , An-Lin Cai  5 , Li Ma  6 , You-Ming Long  7
Affiliations
Case Reports

Neuronal antibody targeting metabotropic glutamate receptor 8 in five cases and its pathogenicity

Pei-Hao Lin et al. J Neurol. .

Abstract

Objective: To characterize patients with autoantibodies against metabotropic glutamate receptor 8 (mGluR8) and assess the pathogenicity of these antibodies.

Methods: Anti-mGluR8 antibodies were detected via cell-based assay and immunoprecipitation. Clinical data from five anti-mGluR8-positive patients and previously reported cases with other anti-mGluR antibodies were reviewed. Patient-derived IgG was purified and absorbed using mGluR8-expressing or control HEK293T cells. Pathogenicity was tested in hippocampal neuron cultures and via passive transfer into mice, with ataxia evaluated using behavioral tests.

Results: Five patients (4 male, median age 61) presented with subacute ataxia; other symptoms included dysarthria, ophthalmoplegia, dysphagia, and cognitive changes. Brain MRI showed cerebellar and cortical atrophy in all cases. Immunotherapy led to transient improvement in all patients, with stabilization in three of four with follow-up. In vitro, non-mGluR8-absorbed IgG reduced synaptic mGluR8 clusters. Mice injected with non-mGluR8-absorbed IgG developed transient ataxia peaking at 3-6 h and resolving within 24 h, correlating with antibody binding to Purkinje cells.

Conclusion: Anti-mGluR8 antibody is a novel possible biomarker for autoimmune ataxia, with its pathogenicity supported by passive transfer models.

Keywords: Anti-mGluR8 antibody; Autoimmune disorder; Cerebellar ataxia; Passive transfer model.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that no competing interests exist. Ethical approval: The Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University, China approved the study protocol (2022-hs-56–02) and the animal experiments (A2023-079). All patients provided informed consent to participate in the study. All animal experiments complied with guidelines for the ethical review of laboratory animal welfare People's Republic of China National Standard (GB/T 35892–2018).

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