Antibodies to recombinant synaptotagmin and calcium channel subtypes in Lambert-Eaton myasthenic syndrome

Takamori, Masaharu; Takahashi, Masami; Yasukawa, Yoshihiro; Iwasa, Kazuo; Nemoto, Yasuo; Suenaga, Akihito; Nagataki, Shigenobu; Nakamura, Tatsufumi

doi:10.1016/0022-510x(95)00162-u

Cited by 54 publications

(20 citation statements)

References 37 publications

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“…21 Basing our choice of the P/Q-type VGCC on these reports, we studied human serum samples by the use of immunoprecipitation assays for which -conotoxin MVIIC-labeled cerebellar extract was used as an antigen. The resulting frequency (80%) of anti-P/Q-type VGCC antibodies in our 30 LEMS patients was as high as those reported previously [6][7][8] (TABLE 1). Seventeen of 24 LEMS patients positive for the antibody had carcinomas, including 15 patients with SCLC (TABLE 1); 2 SCLC patients were without LEMS, but were positive for the antibody (TABLE 2).…”

Section: Antibodies To P/q-type Vgcc In Humanssupporting

confidence: 78%

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a

Takamori

Iwasa

Komai

1998

Annals of the New York Academy of Sciences

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Section: Antibodies To P/q-type Vgcc In Humanssupporting

confidence: 78%

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a

Takamori

Iwasa

Komai

1998

Annals of the New York Academy of Sciences

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“…Eighty-five to ninety percent of LEMS cases are associated with autoantibodies against presynaptic VGCC [91–93], which impair neuromuscular transmission by diminishing the release of acetylcholine. VGCCs consist of four α1 subunits, which form the voltage sensor pore, and accessory subunits β, α2/δ, and γ (Fig.…”

Section: Autoimmune Neuromuscular Junction Disordersmentioning

confidence: 99%

“…Anti-synaptotagmin I antibody has been detected in a small proportion of patients, including several that were anti-VGCC antibody negative [93]. Synaptotagmin I localizes to the synaptic vesicle membrane where it functions as a calcium sensor to regulate neurotransmitter release.…”

Section: Autoimmune Neuromuscular Junction Disordersmentioning

confidence: 99%

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

Sinmaz

Nguyen

Charabati

et al. 2016

J Neuroinflammation

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BackgroundOur knowledge of autoantibody-associated diseases of the central (CNS) and peripheral (PNS) nervous systems has expanded greatly over the recent years. A number of extracellular and intracellular autoantigens have been identified, and there is no doubt that this field will continue to expand as more autoantigens are discovered as a result of improved clinical awareness and methodological practice. In recent years, interest has shifted to uncover the target epitopes of these autoantibodies.Main bodyThe purpose of this review is to discuss the mapping of the epitope targets of autoantibodies in CNS and PNS antibody-mediated disorders, such as N-methyl-D-aspartate receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), leucine-rich glioma-inactivated protein 1 (Lgi1), contactin-associated protein-like 2 (Caspr2), myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP4), 65 kDa glutamic acid decarboxylase (GAD65), acetylcholine receptor (AChR), muscle-specific kinase (MuSK), voltage-gated calcium channel (VGCC), neurofascin (NF), and contactin. We also address the methods used to analyze these epitopes, the relevance of their determination, and how this knowledge can inform studies on autoantibody pathogenicity. Furthermore, we discuss triggers of autoimmunity, such as molecular mimicry, ectopic antigen expression, epitope spreading, and potential mechanisms for the rising number of double autoantibody-positive patients.ConclusionsMolecular insights into specificity and role of autoantibodies will likely improve diagnosis and treatment of CNS and PNS neuroimmune diseases.

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“…The autoantibodies in LEMS, however, are heterogeneous. Antibodies against the other different VGCC subtypes [6,18,21,35], the beta subunits [33] and synaptotagmin [20,37] have been identified in LEMS sera, but their seropositivity is lower than that of the anti-P/Q-type VGCC antibodies. To clarify the pathogenesis of LEMS, we must determine which antibodies are pathogenic against the neuromuscular junction.…”

Section: Discussionmentioning

confidence: 98%

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

Nakao

Motomura

Suenaga

et al. 1999

Journal of Neurology

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An immunoprecipitation assay was used to measure omega-conotoxin MVIIC (P/Q-type) binding and blocking calcium channel antibodies in 67 patients with Lambert-Eaton myasthenic syndrome (LEMS) and in a large control population. We first showed the presence of omega-conotoxin MVIIC-blocking antibody in LEMS patients. Binding antibodies were detected in 55 of 67 (82.1%) LEMS patients and in 2 of 296 (0.7%) controls. In contrast, blocking antibodies were positive in 14 of 67 (20.9%) LEMS patients and 8 of 171 (4.7%) controls. No LEMS patient had negative binding antibodies and positive blocking antibodies. The immunoprecipitation assay detected no antibodies against the whole P/Q-type calcium channel in either the paraneoplastic cerebellar degeneration or the amyotrophic lateral sclerosis sera. Neither the omega-conotoxin MVIIC-binding nor the -blocking calcium channel antibodies were correlated with clinical severity across the individuals, but longitudinal studies of some LEMS patients showed an inverse relation between binding antibody titre and disease severity. We concluded that the 125I-omega-conotoxin MVIIC assay for anti-P/Q-type voltage-gated calcium channel antibodies is highly specific for LEMS and that this sensitive binding antibody assay could be more valuable than the blocking antibody assay in the diagnosis of LEMS.

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Antibodies to recombinant synaptotagmin and calcium channel subtypes in Lambert-Eaton myasthenic syndrome

Cited by 54 publications

References 37 publications

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

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

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Antibodies to recombinant synaptotagmin and calcium channel subtypes in Lambert-Eaton myasthenic syndrome

Cited by 54 publications

References 37 publications

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndromea

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndromea

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

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

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Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a

Antigenic Sites of the Voltage‐gated Calcium Channel in Lambert‐Eaton Myasthenic Syndrome^a