Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice

L. Borradori, J. B. Caldwell, R. A. Briggaman, C. E. Burr, W. R. Gammon, W. D. James, K. B. Yancey

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease. Observations: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride- separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice. Conclusions: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.

Original languageEnglish (US)
Pages (from-to)590-595
Number of pages6
JournalArchives of Dermatology
Volume131
Issue number5
StatePublished - 1995

Fingerprint

Epidermolysis Bullosa Acquisita
Autoantibodies
Collagen Type VII
Skin
Immunoglobulin G
Sodium Chloride
Epidermolysis Bullosa Dystrophica
Syndactyly
Complement Membrane Attack Complex
Light
Antibodies
Immune System Diseases
Blister
Dermis
Indirect Fluorescent Antibody Technique
Scalp
Serum
Autoimmunity
Fluorescence Microscopy
Granulocytes

ASJC Scopus subject areas

  • Dermatology

Cite this

Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice. / Borradori, L.; Caldwell, J. B.; Briggaman, R. A.; Burr, C. E.; Gammon, W. R.; James, W. D.; Yancey, K. B.

In: Archives of Dermatology, Vol. 131, No. 5, 1995, p. 590-595.

Research output: Contribution to journalArticle

Borradori, L. ; Caldwell, J. B. ; Briggaman, R. A. ; Burr, C. E. ; Gammon, W. R. ; James, W. D. ; Yancey, K. B. / Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice. In: Archives of Dermatology. 1995 ; Vol. 131, No. 5. pp. 590-595.
@article{b4689c6b97f44ba480a4d682753d4260,
title = "Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice",
abstract = "Background: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease. Observations: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride- separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice. Conclusions: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.",
author = "L. Borradori and Caldwell, {J. B.} and Briggaman, {R. A.} and Burr, {C. E.} and Gammon, {W. R.} and James, {W. D.} and Yancey, {K. B.}",
year = "1995",
language = "English (US)",
volume = "131",
pages = "590--595",
journal = "JAMA Dermatology",
issn = "2168-6068",
publisher = "American Medical Association",
number = "5",

}

TY - JOUR

T1 - Passive transfer of autoantibodies from a patient with mutilating epidermolysis bullosa acquisita induces specific alterations in the skin of neonatal mice

AU - Borradori, L.

AU - Caldwell, J. B.

AU - Briggaman, R. A.

AU - Burr, C. E.

AU - Gammon, W. R.

AU - James, W. D.

AU - Yancey, K. B.

PY - 1995

Y1 - 1995

N2 - Background: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease. Observations: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride- separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice. Conclusions: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.

AB - Background: Epidermolysis bullosa acquisita is a subepidermal bullous disease characterized by IgG autoantibodies directed against type VII collagen in anchoring fibrils. These autoantibodies are believed to play an important role in the pathogenesis of sub-lamina densa blister formation in this disease. Observations: We describe a patient with epidermolysis bullosa acquisita who has developed mutilating acral involvement with early syndactyly and extensive scarring lesions of the scalp. The patient's serum contains IgG autoantibodies that bind the dermal side of 1-mol/L sodium chloride-separated human skin (at a titer up to 5120), as determined by indirect immunofluorescence microscopy, and type VII collagen, as determined by immunoblot. The severity of this patient's disease and the height of his immune response to type VII collagen prompted us to assess the pathogenicity of his autoantibodies in a murine model. Purified IgG from our patient (or that from a healthy volunteer who served as a control) was administered subcutaneously to BALB/c mice (10 mg/g of body weight) on 2 consecutive days. Light microscopy of normal-appearing skin showed pronounced dermal edema and a dense granulocyte-rich infiltrate in the superficial dermis. Deposits of human IgG, murine C3, and the membrane attack complex of complement were found in the epidermal basement membrane of all experimental mice. Immunogold electron microscopy demonstrated that deposits of human IgG in an experimental subject were localized to anchoring fibrils. Serum samples from mice receiving IgG antibodies from our patient had high titers of circulating antibodies directed against the dermal side of 1-mol/L sodium chloride- separated human skin (titer, 640 to 1280). Light, immunofluorescence, and immunogold electron microscopic studies did not detect such specific alterations in any control mice. Conclusions: Acquired autoimmunity to type VII collagen in patients with epidermolysis bullosa acquisita may result in a clinical phenotype closely resembling that observed in patients with dystrophic epidermolysis bullosa. Passive transfer of purified IgG autoantibodies from a patient with severe epidermolysis bullosa acquisita to BALB/c mice produces histologic and immunopathologic alterations consistent with those seen in patients with this disease.

UR - http://www.scopus.com/inward/record.url?scp=0029046333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029046333&partnerID=8YFLogxK

M3 - Article

C2 - 7741548

AN - SCOPUS:0029046333

VL - 131

SP - 590

EP - 595

JO - JAMA Dermatology

JF - JAMA Dermatology

SN - 2168-6068

IS - 5

ER -