H. Schumann et al., The shed ectodomain of collagen XVII/BP180 is targeted by autoantibodies in different blistering skin diseases, AM J PATH, 156(2), 2000, pp. 685-695
Citations number
43
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Collagen XVII/BP180, an epidermal adhesion molecule, exists as a full-lengt
h transmembrane protein and as a soluble 120-kd ectodomain that is shed fro
m the keratinocyte surface by furin-mediated proteolysis. Despite a number
of studies on autoantibody targets in blistering skin diseases, it has rema
ined unclear whether the physiologically shed ectodomain of collagen XVII p
lays a role as an autoantigen, Here we isolated the authentic, soluble form
of human collagen XVII and showed that it is an autoantigen recognized by
IgG and IgA autoantibodies in different blistering skin diseases and is, in
some cases, the preferential target. The ectodomain was isolated from the
epidermis, keratinocyte media, amniotic fluid, and pemphigoid blister fluid
, and autoantibodies affinity-purified with this ectodomain bound to the pr
oximal surface of the epidermis in normal skin but not in collagen XVII-def
icient skin. The antibody reactivity was not dependent on the native confor
mation or the N-glycosylation of the soluble ectodomain, but was abolished
by collagenase treatment. Sera of 81 patients with a clinically active blis
tering skin disease were reacted with full-length collagen XVII, the authen
tic soluble ectodomain, and recombinant fragments. In bullous and cicatrici
al pemphigoid, IgG reactive with full-length collagen XVII also recognized
the soluble ectodomain, In linear IgA. dermatosis and chronic bullous derma
tosis of childhood, IgA targeted the soluble ectodomain more efficiently th
an the full-length protein. The use of recombinant fragments demonstrated t
hat epitopes were present in several noncollagenous and collagenous subdoma
ins of the molecule, and that a significant portion of the sera targeted Co
l15 domain, a hitherto unrecognized epitope region.