Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes

Vanda A Lennon, Thomas J. Kryzer, Guy E. Griesmann, Padraig E. Suilleabhain, Anthony John Windebank, Andreas Woppmann, George P. Miljanich, Edward H. Lambert

Research output: Contribution to journalArticle

459 Citations (Scopus)

Abstract

Background. Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods. We compared the effects of antagonists of L-type, N- type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results. P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small- cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert- Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma. Conclusions. The high frequency of P/Q-type calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.

Original languageEnglish (US)
Pages (from-to)1467-1474
Number of pages8
JournalNew England Journal of Medicine
Volume332
Issue number22
DOIs
StatePublished - Jun 1 1995

Fingerprint

Lambert-Eaton Myasthenic Syndrome
Paraneoplastic Syndromes
Calcium Channels
Q-Type Calcium Channels
Antibodies
P-Type Calcium Channels
N-Type Calcium Channels
Cultured Cells
Carcinoma
Neoplasms
Small Cell Carcinoma
Antibody Specificity
Myasthenia Gravis
Small Cell Lung Carcinoma
Calcium Channel Blockers
Serum
Autoimmunity
Ion Channels
Cerebral Cortex
Nervous System

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. / Lennon, Vanda A; Kryzer, Thomas J.; Griesmann, Guy E.; Suilleabhain, Padraig E.; Windebank, Anthony John; Woppmann, Andreas; Miljanich, George P.; Lambert, Edward H.

In: New England Journal of Medicine, Vol. 332, No. 22, 01.06.1995, p. 1467-1474.

Research output: Contribution to journalArticle

Lennon, VA, Kryzer, TJ, Griesmann, GE, Suilleabhain, PE, Windebank, AJ, Woppmann, A, Miljanich, GP & Lambert, EH 1995, 'Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes', New England Journal of Medicine, vol. 332, no. 22, pp. 1467-1474. https://doi.org/10.1056/NEJM199506013322203
Lennon, Vanda A ; Kryzer, Thomas J. ; Griesmann, Guy E. ; Suilleabhain, Padraig E. ; Windebank, Anthony John ; Woppmann, Andreas ; Miljanich, George P. ; Lambert, Edward H. / Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. In: New England Journal of Medicine. 1995 ; Vol. 332, No. 22. pp. 1467-1474.
@article{2575afb2d89b4363b0f81bd437290212,
title = "Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes",
abstract = "Background. Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods. We compared the effects of antagonists of L-type, N- type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results. P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small- cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert- Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma. Conclusions. The high frequency of P/Q-type calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.",
author = "Lennon, {Vanda A} and Kryzer, {Thomas J.} and Griesmann, {Guy E.} and Suilleabhain, {Padraig E.} and Windebank, {Anthony John} and Andreas Woppmann and Miljanich, {George P.} and Lambert, {Edward H.}",
year = "1995",
month = "6",
day = "1",
doi = "10.1056/NEJM199506013322203",
language = "English (US)",
volume = "332",
pages = "1467--1474",
journal = "New England Journal of Medicine",
issn = "1533-4406",
publisher = "Massachussetts Medical Society",
number = "22",

}

TY - JOUR

T1 - Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes

AU - Lennon, Vanda A

AU - Kryzer, Thomas J.

AU - Griesmann, Guy E.

AU - Suilleabhain, Padraig E.

AU - Windebank, Anthony John

AU - Woppmann, Andreas

AU - Miljanich, George P.

AU - Lambert, Edward H.

PY - 1995/6/1

Y1 - 1995/6/1

N2 - Background. Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods. We compared the effects of antagonists of L-type, N- type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results. P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small- cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert- Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma. Conclusions. The high frequency of P/Q-type calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.

AB - Background. Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods. We compared the effects of antagonists of L-type, N- type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results. P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small- cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert- Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma. Conclusions. The high frequency of P/Q-type calcium-channel antibodies found in patients with the Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.

UR - http://www.scopus.com/inward/record.url?scp=0029030949&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029030949&partnerID=8YFLogxK

U2 - 10.1056/NEJM199506013322203

DO - 10.1056/NEJM199506013322203

M3 - Article

C2 - 7739683

AN - SCOPUS:0029030949

VL - 332

SP - 1467

EP - 1474

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 1533-4406

IS - 22

ER -