Monoclonal anti acetylcholine receptor antibodies with differing capacities to induce experimental autoimmune myasthenia gravis

C. M. Gomez, David P Richman

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To study the characteristics of the individual autoantibodies that are important in the development of an autoimmune disease, we produced 26 anti-acetylcholine receptor (anti-AChR) monoclonal antibodies (mcAb) and studied the experimental autoimmune myasthenia gravis (EAMG) induced by a number of them. The mcAb reactive with mammalian acetylcholine receptor (M-AChR) exhibited a wide range of dissociation rates from in situ M-AChR of motor endplates. All anti-M-AChR mcAb were capable of producing at least some degree of histopathologic change at the endplate indicative of EAMG, but their potencies varied markedly. One mcAb induced, even at large doses, only minor macrophage invasion without clinical or electromyographic effect. Other induced severe EAMG, and even death, at 1/200th the dose. Low potency was associated with high rate of mcAb dissociation from antigen. High potency was associated with intermediate avidity, not high avidity. These observations suggest that in EAMG, and perhaps in myasthenia gravis, the characteristics of the individual antibodies making up the autoimmune response can determine the severity of the autoimmune disease.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalJournal of Immunology
Volume135
Issue number1
StatePublished - 1985
Externally publishedYes

Fingerprint

Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Monoclonal Antibodies
Antibodies
Autoimmune Diseases
Motor Endplate
Immunologic Techniques
Myasthenia Gravis
Autoimmunity
Autoantibodies
Macrophages
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

@article{f246f2338e3e4df8bc3f7ac666fb189c,
title = "Monoclonal anti acetylcholine receptor antibodies with differing capacities to induce experimental autoimmune myasthenia gravis",
abstract = "To study the characteristics of the individual autoantibodies that are important in the development of an autoimmune disease, we produced 26 anti-acetylcholine receptor (anti-AChR) monoclonal antibodies (mcAb) and studied the experimental autoimmune myasthenia gravis (EAMG) induced by a number of them. The mcAb reactive with mammalian acetylcholine receptor (M-AChR) exhibited a wide range of dissociation rates from in situ M-AChR of motor endplates. All anti-M-AChR mcAb were capable of producing at least some degree of histopathologic change at the endplate indicative of EAMG, but their potencies varied markedly. One mcAb induced, even at large doses, only minor macrophage invasion without clinical or electromyographic effect. Other induced severe EAMG, and even death, at 1/200th the dose. Low potency was associated with high rate of mcAb dissociation from antigen. High potency was associated with intermediate avidity, not high avidity. These observations suggest that in EAMG, and perhaps in myasthenia gravis, the characteristics of the individual antibodies making up the autoimmune response can determine the severity of the autoimmune disease.",
author = "Gomez, {C. M.} and Richman, {David P}",
year = "1985",
language = "English (US)",
volume = "135",
pages = "234--241",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Monoclonal anti acetylcholine receptor antibodies with differing capacities to induce experimental autoimmune myasthenia gravis

AU - Gomez, C. M.

AU - Richman, David P

PY - 1985

Y1 - 1985

N2 - To study the characteristics of the individual autoantibodies that are important in the development of an autoimmune disease, we produced 26 anti-acetylcholine receptor (anti-AChR) monoclonal antibodies (mcAb) and studied the experimental autoimmune myasthenia gravis (EAMG) induced by a number of them. The mcAb reactive with mammalian acetylcholine receptor (M-AChR) exhibited a wide range of dissociation rates from in situ M-AChR of motor endplates. All anti-M-AChR mcAb were capable of producing at least some degree of histopathologic change at the endplate indicative of EAMG, but their potencies varied markedly. One mcAb induced, even at large doses, only minor macrophage invasion without clinical or electromyographic effect. Other induced severe EAMG, and even death, at 1/200th the dose. Low potency was associated with high rate of mcAb dissociation from antigen. High potency was associated with intermediate avidity, not high avidity. These observations suggest that in EAMG, and perhaps in myasthenia gravis, the characteristics of the individual antibodies making up the autoimmune response can determine the severity of the autoimmune disease.

AB - To study the characteristics of the individual autoantibodies that are important in the development of an autoimmune disease, we produced 26 anti-acetylcholine receptor (anti-AChR) monoclonal antibodies (mcAb) and studied the experimental autoimmune myasthenia gravis (EAMG) induced by a number of them. The mcAb reactive with mammalian acetylcholine receptor (M-AChR) exhibited a wide range of dissociation rates from in situ M-AChR of motor endplates. All anti-M-AChR mcAb were capable of producing at least some degree of histopathologic change at the endplate indicative of EAMG, but their potencies varied markedly. One mcAb induced, even at large doses, only minor macrophage invasion without clinical or electromyographic effect. Other induced severe EAMG, and even death, at 1/200th the dose. Low potency was associated with high rate of mcAb dissociation from antigen. High potency was associated with intermediate avidity, not high avidity. These observations suggest that in EAMG, and perhaps in myasthenia gravis, the characteristics of the individual antibodies making up the autoimmune response can determine the severity of the autoimmune disease.

UR - http://www.scopus.com/inward/record.url?scp=0021858279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021858279&partnerID=8YFLogxK

M3 - Article

C2 - 3873489

AN - SCOPUS:0021858279

VL - 135

SP - 234

EP - 241

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -