Anti-basement membrane autoantibodies in patients with anti-epiligrin cicatricial pemphigoid bind the α subunit of laminin 5

G. Kirtschig, M. P. Marinkovich, R. E. Burgeson, K. B. Yancey

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the α subunit of laminin 5 but show no reactivity to its β or γ subunits. In addition, circulating IgG from a representative patient was affinity-purified against the α subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the α subunit of laminin 5 (i.e., laminin subunit α3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit α3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic.

Original languageEnglish (US)
Pages (from-to)543-548
Number of pages6
JournalJournal of Investigative Dermatology
Volume105
Issue number4
StatePublished - 1995

Fingerprint

Benign Mucous Membrane Pemphigoid
Basement Membrane
Autoantibodies
Laminin
Keratinocytes
Disulfides
Skin
Peptides
kalinin
Epidermolysis Bullosa Acquisita
Serum
Monoclonal Antibodies
Patient Advocacy
Bullous Pemphigoid
Antibodies
Blister
Immunoprecipitation
Epidermis
Systemic Lupus Erythematosus
Extracellular Matrix

ASJC Scopus subject areas

  • Dermatology

Cite this

Anti-basement membrane autoantibodies in patients with anti-epiligrin cicatricial pemphigoid bind the α subunit of laminin 5. / Kirtschig, G.; Marinkovich, M. P.; Burgeson, R. E.; Yancey, K. B.

In: Journal of Investigative Dermatology, Vol. 105, No. 4, 1995, p. 543-548.

Research output: Contribution to journalArticle

@article{da317dbd539e4399b96aa5bb0deb88c7,
title = "Anti-basement membrane autoantibodies in patients with anti-epiligrin cicatricial pemphigoid bind the α subunit of laminin 5",
abstract = "Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the α subunit of laminin 5 but show no reactivity to its β or γ subunits. In addition, circulating IgG from a representative patient was affinity-purified against the α subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the α subunit of laminin 5 (i.e., laminin subunit α3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit α3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic.",
author = "G. Kirtschig and Marinkovich, {M. P.} and Burgeson, {R. E.} and Yancey, {K. B.}",
year = "1995",
language = "English (US)",
volume = "105",
pages = "543--548",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Anti-basement membrane autoantibodies in patients with anti-epiligrin cicatricial pemphigoid bind the α subunit of laminin 5

AU - Kirtschig, G.

AU - Marinkovich, M. P.

AU - Burgeson, R. E.

AU - Yancey, K. B.

PY - 1995

Y1 - 1995

N2 - Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the α subunit of laminin 5 but show no reactivity to its β or γ subunits. In addition, circulating IgG from a representative patient was affinity-purified against the α subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the α subunit of laminin 5 (i.e., laminin subunit α3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit α3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic.

AB - Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the α subunit of laminin 5 but show no reactivity to its β or γ subunits. In addition, circulating IgG from a representative patient was affinity-purified against the α subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the α subunit of laminin 5 (i.e., laminin subunit α3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit α3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic.

UR - http://www.scopus.com/inward/record.url?scp=0028793403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028793403&partnerID=8YFLogxK

M3 - Article

VL - 105

SP - 543

EP - 548

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 4

ER -