Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease

Nouha Domloge-Hultsch, W. Ray Gammon, R. A. Briggaman, Susana G. Gil, William G. Carter, Kim B. Yancey

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

Epiligrin, the major component of human keratinocyte extracellular matrix, serves as the preferred integrin ligand for α3β1 in plasma membranes and focal adhesions, and colocalizes with α6β4 in hemidesmosomes. In human skin, epiligrin is found in the lamina lucida subregion of epidermal basement membrane, where it is thought to be associated with anchoring filaments. We have identified three patients with an acquired mucosal predominant subepidermal blistering disease who have IgG anti-basement membrane autoantibodies that bind the lamina lucida/lamina densa interface of epidermal basement membrane, stain cultured human keratinocyte extracellular matrix, and immunoprecipitate disulfide linked polypeptides of 170, 145, 125, and 95 kD in human keratinocyte culture media in a pattern identical to that of P1E1, a murine monoclonal antiepiligrin antibody. Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3 antigen) previously reported to be absent from the skin of patients with lethal junctional epidermolysis bullosa, an inherited subepidermal blistering disease. Moreover, skin from a fetus with this disease shows no evidence of reactivity to patient antiepiligrin autoantibodies or P1E1. These studies show that antiepiligrin autoantibodies are a specific marker for a novel autoimmune blistering disease and that the epidermal basement membrane antigen absent in patients with lethal junctional epidermolysis bullosa is epiligrin.

Original languageEnglish (US)
Pages (from-to)1628-1633
Number of pages6
JournalJournal of Clinical Investigation
Volume90
Issue number4
StatePublished - Oct 1992

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Keratinocytes
Skin Diseases
Integrins
Basement Membrane
Ligands
Junctional Epidermolysis Bullosa
Autoantibodies
Antigens
Skin
Extracellular Matrix
Monoclonal Antibodies
Hemidesmosomes
Focal Adhesions
Immunoprecipitation
Disulfides
Autoimmune Diseases
Culture Media
Fetus
Coloring Agents
Cell Membrane

Keywords

  • Autoimmunity
  • Bullous skin diseases
  • Epidermolysis bullosa
  • Epiligrin
  • Integrin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease. / Domloge-Hultsch, Nouha; Gammon, W. Ray; Briggaman, R. A.; Gil, Susana G.; Carter, William G.; Yancey, Kim B.

In: Journal of Clinical Investigation, Vol. 90, No. 4, 10.1992, p. 1628-1633.

Research output: Contribution to journalArticle

Domloge-Hultsch, Nouha ; Gammon, W. Ray ; Briggaman, R. A. ; Gil, Susana G. ; Carter, William G. ; Yancey, Kim B. / Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 4. pp. 1628-1633.
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