Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes

Diya F. Mutasim, Lynne Morrison, Yuzo Takahashi, Ramzy S. Labib, John Skouge, Luis A. Diaz, Grant J. Anhalt

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Bullous pemphigoid (BP) antibodies are deposited predominantly in the lamina lucida in vivo; however, circulating BP antibodies bind in vitro to the cytoplasmic plaque of basal cell hemidesmosomes. We examined the ability of IgG in nine BP sera to bind to intracellular or extracellular antigen. On skin cryosections, indirect IF showed IgG bound to basement membrane zone (BMZ) and indirect ImmunoEM confirmed intracellular binding on the cytoplasmic plaque of hemidesmosomes. In contrast, when normal skin was exposed to BP serum in organ culture, direct IF showed fainter linear deposition of IgG along the BMZ, and direct ImmunoEM demonstrated extracellular IgG binding in the lamina lucida, predominantly beneath hemidesmosomes. Four of nine sera showed complement fixation on indirect IF samples (IgG bound to intracellular antigen) and three showed complement fixation on direct IF specimens (IgG bound to extracelluar antigen). Three of the nine sera con tained complement fixing antibodies detectable only in antibody populations specific for intracellular or extracellular antigen. Western immunoblots showed that five of nine sera recognized a 240-kD protein and four of nine recognized a 180-kD protein. There was no correlation between the presence (or absence) of either band and the detection of complement fixing antibodies specific for intracellular or extracellular antigen. BP autoantibodies bind both intracellular and extracellular antigen, and IgG binding exclusively to extracellular antigen that mimics the in vivo situation can be detected by using organ culture. Complement fixation may be restricted to antibodies specific for intracellular or extracellular antigen. These findings underscore the complexity of the autoantibody-antigen system in BP and have implications regarding the proposed pathogenicity of the autoantibodies.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalJournal of Investigative Dermatology
Volume92
Issue number2
StatePublished - Feb 1989
Externally publishedYes

Fingerprint

Hemidesmosomes
Bullous Pemphigoid
Antigens
Immunoglobulin G
Antibodies
Autoantibodies
Serum
Organ Culture Techniques
Basement Membrane
Skin
Virulence
Proteins
Western Blotting
Cells

ASJC Scopus subject areas

  • Dermatology

Cite this

Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes. / Mutasim, Diya F.; Morrison, Lynne; Takahashi, Yuzo; Labib, Ramzy S.; Skouge, John; Diaz, Luis A.; Anhalt, Grant J.

In: Journal of Investigative Dermatology, Vol. 92, No. 2, 02.1989, p. 225-230.

Research output: Contribution to journalArticle

Mutasim, Diya F. ; Morrison, Lynne ; Takahashi, Yuzo ; Labib, Ramzy S. ; Skouge, John ; Diaz, Luis A. ; Anhalt, Grant J. / Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes. In: Journal of Investigative Dermatology. 1989 ; Vol. 92, No. 2. pp. 225-230.
@article{fed6a58c297a45eb99b81c5e44162374,
title = "Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes",
abstract = "Bullous pemphigoid (BP) antibodies are deposited predominantly in the lamina lucida in vivo; however, circulating BP antibodies bind in vitro to the cytoplasmic plaque of basal cell hemidesmosomes. We examined the ability of IgG in nine BP sera to bind to intracellular or extracellular antigen. On skin cryosections, indirect IF showed IgG bound to basement membrane zone (BMZ) and indirect ImmunoEM confirmed intracellular binding on the cytoplasmic plaque of hemidesmosomes. In contrast, when normal skin was exposed to BP serum in organ culture, direct IF showed fainter linear deposition of IgG along the BMZ, and direct ImmunoEM demonstrated extracellular IgG binding in the lamina lucida, predominantly beneath hemidesmosomes. Four of nine sera showed complement fixation on indirect IF samples (IgG bound to intracellular antigen) and three showed complement fixation on direct IF specimens (IgG bound to extracelluar antigen). Three of the nine sera con tained complement fixing antibodies detectable only in antibody populations specific for intracellular or extracellular antigen. Western immunoblots showed that five of nine sera recognized a 240-kD protein and four of nine recognized a 180-kD protein. There was no correlation between the presence (or absence) of either band and the detection of complement fixing antibodies specific for intracellular or extracellular antigen. BP autoantibodies bind both intracellular and extracellular antigen, and IgG binding exclusively to extracellular antigen that mimics the in vivo situation can be detected by using organ culture. Complement fixation may be restricted to antibodies specific for intracellular or extracellular antigen. These findings underscore the complexity of the autoantibody-antigen system in BP and have implications regarding the proposed pathogenicity of the autoantibodies.",
author = "Mutasim, {Diya F.} and Lynne Morrison and Yuzo Takahashi and Labib, {Ramzy S.} and John Skouge and Diaz, {Luis A.} and Anhalt, {Grant J.}",
year = "1989",
month = "2",
language = "English (US)",
volume = "92",
pages = "225--230",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Definition of bullous pemphigoid antibody binding to intracellular and extracellular antigen associated with hemidesmosomes

AU - Mutasim, Diya F.

AU - Morrison, Lynne

AU - Takahashi, Yuzo

AU - Labib, Ramzy S.

AU - Skouge, John

AU - Diaz, Luis A.

AU - Anhalt, Grant J.

PY - 1989/2

Y1 - 1989/2

N2 - Bullous pemphigoid (BP) antibodies are deposited predominantly in the lamina lucida in vivo; however, circulating BP antibodies bind in vitro to the cytoplasmic plaque of basal cell hemidesmosomes. We examined the ability of IgG in nine BP sera to bind to intracellular or extracellular antigen. On skin cryosections, indirect IF showed IgG bound to basement membrane zone (BMZ) and indirect ImmunoEM confirmed intracellular binding on the cytoplasmic plaque of hemidesmosomes. In contrast, when normal skin was exposed to BP serum in organ culture, direct IF showed fainter linear deposition of IgG along the BMZ, and direct ImmunoEM demonstrated extracellular IgG binding in the lamina lucida, predominantly beneath hemidesmosomes. Four of nine sera showed complement fixation on indirect IF samples (IgG bound to intracellular antigen) and three showed complement fixation on direct IF specimens (IgG bound to extracelluar antigen). Three of the nine sera con tained complement fixing antibodies detectable only in antibody populations specific for intracellular or extracellular antigen. Western immunoblots showed that five of nine sera recognized a 240-kD protein and four of nine recognized a 180-kD protein. There was no correlation between the presence (or absence) of either band and the detection of complement fixing antibodies specific for intracellular or extracellular antigen. BP autoantibodies bind both intracellular and extracellular antigen, and IgG binding exclusively to extracellular antigen that mimics the in vivo situation can be detected by using organ culture. Complement fixation may be restricted to antibodies specific for intracellular or extracellular antigen. These findings underscore the complexity of the autoantibody-antigen system in BP and have implications regarding the proposed pathogenicity of the autoantibodies.

AB - Bullous pemphigoid (BP) antibodies are deposited predominantly in the lamina lucida in vivo; however, circulating BP antibodies bind in vitro to the cytoplasmic plaque of basal cell hemidesmosomes. We examined the ability of IgG in nine BP sera to bind to intracellular or extracellular antigen. On skin cryosections, indirect IF showed IgG bound to basement membrane zone (BMZ) and indirect ImmunoEM confirmed intracellular binding on the cytoplasmic plaque of hemidesmosomes. In contrast, when normal skin was exposed to BP serum in organ culture, direct IF showed fainter linear deposition of IgG along the BMZ, and direct ImmunoEM demonstrated extracellular IgG binding in the lamina lucida, predominantly beneath hemidesmosomes. Four of nine sera showed complement fixation on indirect IF samples (IgG bound to intracellular antigen) and three showed complement fixation on direct IF specimens (IgG bound to extracelluar antigen). Three of the nine sera con tained complement fixing antibodies detectable only in antibody populations specific for intracellular or extracellular antigen. Western immunoblots showed that five of nine sera recognized a 240-kD protein and four of nine recognized a 180-kD protein. There was no correlation between the presence (or absence) of either band and the detection of complement fixing antibodies specific for intracellular or extracellular antigen. BP autoantibodies bind both intracellular and extracellular antigen, and IgG binding exclusively to extracellular antigen that mimics the in vivo situation can be detected by using organ culture. Complement fixation may be restricted to antibodies specific for intracellular or extracellular antigen. These findings underscore the complexity of the autoantibody-antigen system in BP and have implications regarding the proposed pathogenicity of the autoantibodies.

UR - http://www.scopus.com/inward/record.url?scp=0024582512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024582512&partnerID=8YFLogxK

M3 - Article

VL - 92

SP - 225

EP - 230

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 2

ER -