Specificity of ω-conotoxin MVIIC-binding and -blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome

Nakao, Yoshio; Motomura, Masakatsu; Suenaga, Akihito; Nakamura, Tatsufumi; Yoshimura, Tsuyoshi; Tsujihata, Mitsuhiro; Mori, Masataka; Itoh, Masao; Nagataki, Shigenobu

doi:10.1007/s004150050303

Cited by 18 publications

(11 citation statements)

References 37 publications

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“…Our study showed that anti-P/Q-type VGCC antibodies were detected in 85% of patients with LEMS. 13 In our results, it was surprising that 9% of our LEMS patients are associated with cerebellar ataxia.…”

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confidence: 84%

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Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome

Fukuda

Motomura

Nakao

et al. 2002

Annals of Neurology

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125

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The aim of this study was to clarify whether autoimmunity against P/Q-type voltage-gated calcium channels (VGCCs) in the cerebellum was associated with the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome (LEMS). We used human autopsy cerebellar tissues from three PCD-LEMS patients and six other disease patients including one with LEMS as the controls. We compared cerebellar P/Q-type VGCC in these patients and controls for the amount and ratio of autoantibody-channel complex using an 125I-omega-conotoxin MVIIC-binding assay with Scatchard analysis, and their distribution using autoradiography. The quantity of cerebellar P/Q-type VGCC measured by Scatchard analysis were reduced in PCD-LEMS patients (63.0 +/- 7.0 fmol/mg, n = 3), compared with the controls (297.8 +/- 38.9 fmol/mg, n = 6). The ratio of autoantibody-VGCC complexes to total P/Q-type VGCCs measured by immunoprecipitation assay were increased in PCD-LEMS patients. We analysed cerebellar specimens by autoradiography using (125)I-omega-conotoxin MVIIC, which specifically binds to P/Q-type VGCCs. In PCD-LEMS cerebellum, the toxin binding sites of P/Q-type VGCCs were markedly reduced compared with controls, especially in the molecular layer, which is the richest area of P/Q-type VGCCs in the normal cerebellum. This suggests that P/Q-type VGCCs of the cerebellar molecular layer is the immunological target in developing PCD-LEMS.

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confidence: 84%

“…Synthetic -conotoxin MVIIC purchased from the Peptide Institute (Osaka, Japan) was iodinated with 125 I (Nakao and colleagues 13 ). The specific activity was 2,000Ci/mmol.…”

Section: Binding Studiesmentioning

confidence: 99%

Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome

Fukuda

Motomura

Nakao

et al. 2002

Annals of Neurology

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125

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“…Recently, antibodies to the P/Q‐type VGCC (16–18), rather than L‐type (19) or N‐type (20,21), were identified in a high frequency in patients with LEMS. Moreover, recent findings indicated that the P/Q‐type rather than the N‐type VGCC is responsible for the control of neurotransmitter release at the human neuromuscular junctions (22).…”

Section: Autoantibodies In Lemsmentioning

confidence: 99%

Apheresis Treatment in Lambert‐Eaton Myasthenic Syndrome

Motomura

Hamasaki

Nakane

et al. 2000

Therapeutic Apheresis

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The Lambert‐Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q‐type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti‐P/Q‐type voltage‐gated calcium channel (P/Q‐VGCC) antibody. The first case, a 72‐year‐old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q‐VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti‐P/Q‐VGCC antibody titers. The second case, a 73‐year‐old male presenting with leg weakness, was treated by PE and double‐filtration plasmapheresis. The P/Q‐VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q‐VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.

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“…4,5 Patients with titers less than three standard deviations above the mean for the normal controls were classified as seronegative. The study was based on a large cohort of LEMS patients seen by a Japanese neurologist between 1992 and 1999.…”

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Seronegative Lambert-Eaton myasthenic syndrome

Nakao¹,

Motomura²,

Fukudome³

et al. 2002

Neurology

115

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The authors characterized the clinical and immunologic features of 110 patients with Lambert-Eaton myasthenic syndrome (LEMS). Anti-P/Q-type voltage-gated calcium channels (VGCC) antibodies were detected in 85% of the patients (seropositive) but not in the rest (seronegative). Except for the indication that small cell lung carcinoma is less common in seronegative patients, no significant differences were found in the clinical characteristics of patients who had or did not have anti-P/Q-type VGCC antibodies. The results of passive transfer experiments suggest that seronegative LEMS is also an autoantibody-mediated disorder.

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Specificity of ω-conotoxin MVIIC-binding and -blocking calcium channel antibodies in Lambert-Eaton myasthenic syndrome

Cited by 18 publications

References 37 publications

Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome

Reduction of P/Q‐type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert‐Eaton myasthenic syndrome

Apheresis Treatment in Lambert‐Eaton Myasthenic Syndrome

Seronegative Lambert-Eaton myasthenic syndrome

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