The shed ectodomain of collagen XVII/BP180 is targeted by autoantibodies in different blistering skin diseases

Hauke Schumann, Jens Baetge, Kaisa Tasanen, Fenella Wojnarowska, Heike Schäcke, Detlef Zillikens, Leena Bruckner-Tuderman*

*Corresponding author for this work
    157 Citations (Scopus)


    Collagen XVII/BP180, an epidermal adhesion molecule, exists as a full-length transmembrane protein and as a soluble 120-kd ectodomain that is shed from the keratinocyte surface by furin-mediated proteolysis. Despite a number of studies on autoantibody targets in blistering skin diseases, it has remained unclear whether the physiologically shed ectodomain of collagen XVII plays 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 proximal surface of the epidermis in normal skin but not in collagen XVII-deficient skin. The antibody reactivity was not dependent on the native conformation or the N-glycosylation of the soluble ectodomain, but was abolished by collagenase treatment. Sera of 81 patients with a clinically active blistering skin disease were reacted with full-length collagen XVII, the authentic soluble ectodomain, and recombinant fragments. In bullous and cicatricial pemphigoid, IgG reactive with full-length collagen XVII also recognized the soluble ectodomain. In linear IgA dermatosis and chronic bullous dermatosis of childhood, IgA targeted the soluble ectodomain more efficiently than the full-length protein. The use of recombinant fragments demonstrated that epitopes were present in several noncollagenous and collagenous subdomains of the molecule, and that a significant portion of the sera targeted Col15 domain, a hitherto unrecognized epitope region.

    Original languageEnglish
    JournalAmerican Journal of Pathology
    Issue number2
    Pages (from-to)685-695
    Number of pages11
    Publication statusPublished - 2000


    Dive into the research topics of 'The shed ectodomain of collagen XVII/BP180 is targeted by autoantibodies in different blistering skin diseases'. Together they form a unique fingerprint.

    Cite this