TY - JOUR
T1 - Epiligrin, the major human keratinocyte integrin ligand, is a target in both an acquired autoimmune and an inherited subepidermal blistering skin disease
AU - Domloge-Hultsch, Nouha
AU - Gammon, W. Ray
AU - Briggaman, R. A.
AU - Gil, Susana G.
AU - Carter, William G.
AU - Yancey, Kim B.
PY - 1992/10
Y1 - 1992/10
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Bullous skin diseases
KW - Epidermolysis bullosa
KW - Epiligrin
KW - Integrin
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U2 - 10.1172/JCI116033
DO - 10.1172/JCI116033
M3 - Article
C2 - 1401088
AN - SCOPUS:0026459877
SN - 0021-9738
VL - 90
SP - 1628
EP - 1633
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 4
ER -