Lambert–Eaton syndrome antibodies target multiple subunits of voltage‐gated Ca<sup>2+</sup> channels

Hajela, Ravindra K.; Huntoon, Kristin; Atchison, William D.

doi:10.1002/mus.24295

Cited by 12 publications

(6 citation statements)

References 56 publications

(68 reference statements)

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“…Hajela and coworkers 36 reported that multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS. Autoantibodies from patients with LEMS bind directly to multiple VGCC a1 subunits and the b3 subunit.…”

Section: Diagnosismentioning

confidence: 99%

Lambert-Eaton Myasthenic Syndrome

Kesner¹,

Dimachkie

et al. 2018

Neurologic Clinics

101

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Lambert-Eaton myasthenic syndrome is a paraneoplastic or primary autoimmune neuromuscular junction disorder characterized by proximal weakness, autonomic dysfunction and ariflexia. The characteristic symptoms are thought to be caused by antibodies generated against the P/Q-type voltage-gated calcium channels present on presynaptic nerve terminals and by diminished release of acetylcholine. More than half of Lambert-Eaton myasthenic syndrome cases are associated with small cell lung carcinoma. Diagnosis is confirmed by serologic testing and electrophysiologic studies. 3,4-diaminopyridine is effective symptomatic treatment of LEMS.

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Section: Diagnosismentioning

confidence: 99%

Lambert-Eaton Myasthenic Syndrome

Kesner¹,

Dimachkie

et al. 2018

Neurologic Clinics

101

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“…While two studies detected antibodies against VGCC subunit other than alpha-1 in a subset of patients with LEMS [ 142 – 144 ], no reactivity to the β4 or γ2 auxiliary subunits of VGCC was found in sera from PCD patients in a HEK293 CBA [ 141 ]. However, the authors of the latter study identified in a single patient with SCLC-associated PCD and anti-P/Q-type VGCC a novel autoantibody to the cytoskeletal matrix of the nerve terminals active zone (CAZ) protein ELKS1 (also termed ERC1) [ 141 ], which was recently shown to interact and co-localise with the auxiliary β4 subunit of VGCC [ 145 ].…”

Section: Anti-vgccmentioning

confidence: 99%

‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC

Jarius

Wildemann

2015

J Neuroinflammation

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Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as ‘Medusa head antibodies’ due their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects, and provides a summary and outlook.

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“…Menos del 10% de pacientes con SMLE pueden desarrollar degeneración cerebelosa manifestando ataxia, encefalitis límbica y neuropatía sensorial (8,14,15,16). Dentro de las disfunciones autonómicas que se describen se encuentran constipación, alteración pupilomotora, xerostomía, disfunción erectil y anormalidades en la sudoración hasta en un 30% de los pacientes (1,2,5,15,17). Algunos síntomas constitucionales pueden estar presentes como parte de la malignidad subyacente, como lo son pérdida de peso y anorexia (10,16).…”

Section: Presentación Clínicaunclassified

“…Las células cancerígenas sobreexpresan distintos tipos de canales de calcio voltage dependientes, por lo que se cree que en respuesta inmune ante estas células se liberan anticuerpos contra estos canales. Sin embargo los anticuerpos no distiguen entre céulas cancerígenas y células sanas (14,17,19). Estos autoanticuerpos interfieren en la terminal nerviosa motora, rica en canales de calcio voltaje dependientes que participan en la transmisión de la señal nerviosa presináptica hacia el músculo esquelético mediada por acetilcolina, lo que provoca un deterioro de la contracción muscular y por ende provoca la sintomatología del paciente (2,13,15,17,18).…”

Section: Diagnosticounclassified

Síndrome de Lambert-Eaton paraneoplásico en carcinoma de células pequeñas de pulmón

2020

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El síndrome miasténico de Lambert Eaton es una patología autoinmune paraneoplásica asociada mayormente a cáncer de pulmón, que se manifiesta con afectación de la unión neuromuscular y disfunciones autonómicas. Se presenta el caso de una paciente femenina de 58 años quien fue diagnosticada con cáncer de pulmón de células pequeñas y que posteriormente presentó la tríada clásica de síndrome miasténico de Lambert Eaton (debilidad proximal de miembros inferiores, disfunción autonómica e hiporreflexia). Se abordó mediante pruebas neurofisiológicas (electromiografía), confirmando su diagnóstico en asociación con el cuadro clínico. El caso presentado a continuación destaca la asociación de neoplasias pulmonares con el diagnóstico de síndrome miasténico de Lambert Eaton y la mejoría de los síntomas gracias al tratamiento sintomático y oncológico.

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Lambert–Eaton syndrome antibodies target multiple subunits of voltage‐gated Ca²⁺ channels

Abstract: Autoantibodies from LEMS patients bind directly to multiple VGCC α(1) subunits as well as the β(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS.

Cited by 12 publications

References 56 publications

Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton Myasthenic Syndrome

‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC

Síndrome de Lambert-Eaton paraneoplásico en carcinoma de células pequeñas de pulmón

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Lambert–Eaton syndrome antibodies target multiple subunits of voltage‐gated Ca2+ channels

Abstract: Autoantibodies from LEMS patients bind directly to multiple VGCC α(1) subunits as well as the β(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS.

Cited by 12 publications

References 56 publications

Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton Myasthenic Syndrome

‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC

Síndrome de Lambert-Eaton paraneoplásico en carcinoma de células pequeñas de pulmón

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Lambert–Eaton syndrome antibodies target multiple subunits of voltage‐gated Ca²⁺ channels