Characteristics in limbic encephalitis with anti–adenylate kinase 5 autoantibodies

Do, Le-Duy; Chanson, Eve; Desestret, Virginie; Joubert, Bastien; Ducray, François; Brugière, Sabine; Couté, Yohann; Formaglio, Maïté; Rogemond, Véronique; Thomas‐Antérion, Catherine; Borrega, Laura; Laurens, Brice; Tison, François; Curot, Jonathan; Brouker, Thomas de; Lebrun-Frénay, Christine; Delattre, Jean‐Yves; Antoine, Jean‐Christophe; Honnorat, Jérôme

doi:10.1212/wnl.0000000000003586

Cited by 56 publications

(29 citation statements)

References 21 publications

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“…As immunostaining on living neurons was negative, the absence of direct interaction between Abs and the antigen is probable explaining the absence of pathogenic effect. This result is similar to other onconeural Abs targeting intracellular antigens [19,20]. …”

Section: Discussionsupporting

confidence: 89%

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration

Gupton

Tanji

et al. 2018

Cerebellum

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Objective: To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Methods: Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67 and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. Results: We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Interpretation: Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.

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Section: Discussionsupporting

confidence: 89%

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration

Gupton

Tanji

et al. 2018

Cerebellum

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“…Results from studies from the past 5 years suggest that 18 F-FDG-PET imaging might be more sensitive than MRI to show an increase in FDG uptake in normal-appearing medial temporal lobes. 28 None identified NA Note: AK5 = adenylate kinase 5, ALE = autoimmune limbic encephalitis, AMPAR = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, CASPR2 = contactinassociated protein-like 2, CRMP5 = collapsin response mediator protein 5, GABABR = γ-aminobutyric acid B receptor, GAD = glutamic acid decarboxylase, LGI-1 = leucine-rich glioma inactivated 1, mGluR5 = metabotropic glutamate receptor 5, NA = not applicable, NMDAR = N-methyl-d-aspartate receptor, SCLC = small-cell lung cancer. *Antibodies in bold are major diagnostic considerations in patients with ALE.…”

Section: Box 2: Diagnostic Criteria For Definite Autoimmune Limbic Enmentioning

confidence: 99%

Diagnosing autoimmune limbic encephalitis

Budhram

Leung

Nicolle

et al. 2019

CMAJ

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“…The target molecules can be localized intracellular or extracellular (9, 98). Some of the intracellular antigens are nuclear proteins.…”

Section: Specific Diseasesmentioning

confidence: 99%

Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

Weissert

2017

Front. Immunol.

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There are common aspects and mechanisms between different types of autoimmune diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), and autoimmune encephalitis (AE) as well as paraneoplastic inflammatory disorders of the central nervous system. To our present knowledge, depending on the disease, T and B cells as well as antibodies contribute to various aspects of the pathogenesis. Possibly the events leading to the breaking of tolerance between the different diseases are of great similarity and so far, only partially understood. Beside endogenous factors (genetics, genomics, epigenetics, malignancy) also exogenous factors (vitamin D, sun light exposure, smoking, gut microbiome, viral infections) contribute to susceptibility in such diseases. What differs between these disorders are the target molecules of the immune attack. For T cells, these target molecules are presented on major histocompatibility complex (MHC) molecules as MHC-bound ligands. B cells have an important role by amplifying the immune response of T cells by capturing antigen with their surface immunoglobulin and presenting it to T cells. Antibodies secreted by plasma cells that have differentiated from B cells are highly structure specific and can have important effector functions leading to functional impairment or/and lesion evolvement. In MS, the target molecules are mainly myelin- and neuron/axon-derived proteins; in NMOSD, mainly aquaporin-4 expressed on astrocytes; and in AE, various proteins that are expressed by neurons and axons.

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Characteristics in limbic encephalitis with anti–adenylate kinase 5 autoantibodies

Abstract: AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage.

Cited by 56 publications

References 21 publications

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration

Diagnosing autoimmune limbic encephalitis

Adaptive Immunity Is the Key to the Understanding of Autoimmune and Paraneoplastic Inflammatory Central Nervous System Disorders

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