ITPR1 autoimmunity: Frequency, neurologic phenotype, and cancer association

Alfugham, Nora; Gadoth, Avi; Lennon, Vanda A.; Komorowski, Lars; Scharf, Madeleine; Hinson, Shannon R.; McKeon, Andrew; Pittock, Sean J.

doi:10.1212/nxi.0000000000000418

Cited by 30 publications

(41 citation statements)

References 7 publications

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“…Anti-PC antibodies mainly react with antigens in the cytoplasm and dendrites of PCs, so they have certain similarities in the morphology of IHC and are often discussed together. The properties of some anti-PCs antibodies reported are shown in Table 2 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In addition, we also recognize that there are some unknown antibodies associated with ACA.…”

Section: Discussionmentioning

confidence: 89%

Autoimmune cerebellar ataxia associated with anti-Purkinje cells antibodies: the next frontier of neuroimmunology

Zhang¹,

Ren²,

Ren³

et al. 2023

Ann Transl Med

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Autoimmune cerebellar ataxia (ACA) is an important cause of sporadic cerebellar ataxia.Technological innovation promotes the rapid development of cerebellar autoimmunity researches in recent years. More and more new antibodies have been proposed to be associated with ACA. Several autoantibodies against Purkinje cells (PCs) have been identified, which constitute the main components. These autoantigens are mainly located in the cytoplasm and dendrites of PCs, and exhibit a specific morphology in immunohistochemistry (IHC). Although the clinical features are relatively homogeneous, there were still some differences among different antibodies. Due to the lack of understanding of the disease and the limited detection technology, it is really difficult to diagnose and manage at present. However, unlike the most of hereditary ataxias, ACA is treatable, and even the neurological dysfunction of some patients may be reversible. Therefore, promptly identification, diagnosis and treatment may benefit some patients. Thus, this article elaborates on the clinical manifestations and laboratory characteristics of anti-PCs-antibodyassociated ACA in order to help neurologists to understand ACA more comprehensively. At the same time, combining our previous exploratory work as well as the technology available, we try to propose a diagnostic strategy for ACA the text and the relevant differential diagnosis was illustrated in detail.

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Section: Discussionmentioning

confidence: 89%

Autoimmune cerebellar ataxia associated with anti-Purkinje cells antibodies: the next frontier of neuroimmunology

Zhang¹,

Ren²,

Ren³

et al. 2023

Ann Transl Med

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“…The largest cohort of patients described with ITPR1-IgG antibodies included five who presented with cerebellar ataxia at an average age of 64 ( 22 ). Of the five patients with CSF available, four had abnormalities such as pleocytosis or elevated protein.…”

Section: Methodsmentioning

confidence: 99%

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia

Garza¹,

Piquet²

2021

Front. Neurol.

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Movement disorders are a common feature of many antibody-associated neurological disorders. In fact, cerebellar ataxia is one of the most common manifestations of autoimmune neurological diseases. Some of the first autoantibodies identified against antigen targets include anti-neuronal nuclear antibody type 1 (ANNA-1 or anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1) also known as anti-Yo have been identified in paraneoplastic cerebellar degeneration. Historically these antibodies have been associated with an underlying malignancy; however, recently discovered antibodies can occur in the absence of cancer as well, resulting in the clinical syndrome of autoimmune cerebellar ataxia. The pace of discovery of new antibodies associated with autoimmune or paraneoplastic cerebellar ataxia has increased rapidly over the last few years, and pathogenesis and potential treatment options remains to be explored. Here we will review the literature on recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia including adaptor protein-3B2 (AP3B2); inositol 1,4,5-trisphophate receptor type 1 (ITPR1); tripartite motif-containing (TRIM) proteins 9, 67, and 46; neurochondrin; neuronal intermediate filament light chain (NIF); septin 5; metabotropic glutamate receptor 2 (mGluR2); seizure-related 6 homolog like 2 (SEZ6L2) and homer-3 antibodies. We will review their clinical characteristics, imaging and CSF findings and treatment response. In addition, we will discuss two clinical case examples of autoimmune cerebellar ataxia.

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“…Association of the neuronal (type 1) isoform of the ubiquitously expressed inositol trisphosphate receptor (ITPR1) with neurological disease was recently identified in this manner, through a study of 14 affected patients. 45 Leading accompanying clinical features in these patients included peripheral neuropathy, cerebellar ataxia, myelopathy, seizures, and encephalopathy. Association with underlying cancer was common and included renal, breast, and lung carcinomas, frequently in the presence of advanced/metastatic disease.…”

Section: Antibodies Directed Against Intraneuronal Antigensmentioning

confidence: 99%

Antibodies in Autoimmune Human Neurological Disease: Pathogenesis and Immunopathology

2018

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Immune-mediated processes represent a rapidly expanding categorical etiology for neurological disease manifestations spanning all subspecialties of neurology. Neural autoantibodies can be grossly divided into two main groups based on localization of the antigen: intracellular and cell membrane/synaptic antibodies. Antibodies reactive with neuronal membrane antigens have been identified in serum and cerebrospinal fluid of patients developing neurological disease either independent of or associated with cancer comorbidity, whereas antibodies directed against intracellular targets have a much higher rate of associated malignancy. Antibodies to neuronal membrane proteins such as the N-methyl-D-aspartate (NMDA) receptor are considered directly pathogenic based on disease models. Similar evidence exists for far fewer autoantibodies directed against intracellular targets. Attempts to produce an antibody-mediated animal model of human paraneoplastic disease have been unsuccessful to date. In this article, we review antineural antibodies and their clinical associations, briefly discuss recently characterized entities, and present proposed mechanisms of antibody pathogenicity.

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ITPR1 autoimmunity: Frequency, neurologic phenotype, and cancer association

Cited by 30 publications

References 7 publications

Autoimmune cerebellar ataxia associated with anti-Purkinje cells antibodies: the next frontier of neuroimmunology

Autoimmune cerebellar ataxia associated with anti-Purkinje cells antibodies: the next frontier of neuroimmunology

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia

Antibodies in Autoimmune Human Neurological Disease: Pathogenesis and Immunopathology

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