Recombinant human acetylcholine receptor α-subunit induces chronic experimental autoimmune myasthenia gravis

Vanda A Lennon, E. H. Lambert, K. R. Leiby, T. B. Okarma, S. Talib

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

A synthetic gene encoding the 210 N-terminal residues of the α-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human α1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 μg. With 6.6 to 22 μg, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 μg or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the α1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

Original languageEnglish (US)
Pages (from-to)2245-2248
Number of pages4
JournalJournal of Immunology
Volume146
Issue number7
StatePublished - 1991

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Autoantibodies
Plasmids
Escherichia coli
Synthetic Genes
Pertussis Vaccine
Bordetella pertussis
Myasthenia Gravis
Autoantigens
Nicotinic Receptors
Emulsions
Population Groups
Recombinant Proteins
Codon
Skeletal Muscle
Proteins
Incidence
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Recombinant human acetylcholine receptor α-subunit induces chronic experimental autoimmune myasthenia gravis. / Lennon, Vanda A; Lambert, E. H.; Leiby, K. R.; Okarma, T. B.; Talib, S.

In: Journal of Immunology, Vol. 146, No. 7, 1991, p. 2245-2248.

Research output: Contribution to journalArticle

Lennon, Vanda A ; Lambert, E. H. ; Leiby, K. R. ; Okarma, T. B. ; Talib, S. / Recombinant human acetylcholine receptor α-subunit induces chronic experimental autoimmune myasthenia gravis. In: Journal of Immunology. 1991 ; Vol. 146, No. 7. pp. 2245-2248.
@article{58a6722b52324d0a92fe4fd6ed082c32,
title = "Recombinant human acetylcholine receptor α-subunit induces chronic experimental autoimmune myasthenia gravis",
abstract = "A synthetic gene encoding the 210 N-terminal residues of the α-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human α1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100{\%} incidence was 2.2 μg. With 6.6 to 22 μg, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 μg or more were more uniformly severe and persistent, with 33{\%} fatality. Rats receiving a control extract of E. coli containing plasmid without the α1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.",
author = "Lennon, {Vanda A} and Lambert, {E. H.} and Leiby, {K. R.} and Okarma, {T. B.} and S. Talib",
year = "1991",
language = "English (US)",
volume = "146",
pages = "2245--2248",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Recombinant human acetylcholine receptor α-subunit induces chronic experimental autoimmune myasthenia gravis

AU - Lennon, Vanda A

AU - Lambert, E. H.

AU - Leiby, K. R.

AU - Okarma, T. B.

AU - Talib, S.

PY - 1991

Y1 - 1991

N2 - A synthetic gene encoding the 210 N-terminal residues of the α-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human α1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 μg. With 6.6 to 22 μg, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 μg or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the α1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

AB - A synthetic gene encoding the 210 N-terminal residues of the α-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human α1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 μg. With 6.6 to 22 μg, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 μg or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the α1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.

UR - http://www.scopus.com/inward/record.url?scp=0025857369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025857369&partnerID=8YFLogxK

M3 - Article

VL - 146

SP - 2245

EP - 2248

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -