The 120-kDa soluble ectodomain of type XVII collagen is recognized by autoantibodies in patients with pemphigoid and linear IgA dermatosis.
BACKGROUND
Type XVII collagen promotes adhesion of basal keratinocytes to epidermal basement membrane, and is the target of disease in patients with certain inherited or acquired blistering diseases. Two forms of type XVII collagen are produced by cultured human keratinocytes: a 180-kDa full-length, transmembrane protein, and a recently identified 120-kDa soluble fragment that corresponds to its collagenous ectodomain.


OBJECTIVE
We aimed to determine the incidence and pattern of reactivity of autoantibodies against the 180- and 120-kDa forms of type XVII collagen in sera from 40 patients with bullous pemphigoid (BP), pemphigoid gestationis or cicatricial pemphigoid (CP), as well as six patients with linear IgA dermatosis (LAD).


METHODS
Various immunochemical techniques were used.


RESULTS
These studies found that the 120-kDa fragment of type XVII collagen was bound by circulating autoantibodies in 13 of 38 patients with BP or CP and all six patients with LAD. While many pemphigoid sera had specific reactivity against one but not both forms of this protein, autoantibodies from patients with LAD bound only the soluble ectodomain.


CONCLUSIONS
These findings are consistent with the presence of both neoepitopes and cross-reactive epitopes on the ectodomain of type XVII collagen. The finding that sera from patients with LAD showed specific reactivity to epidermal basement membrane suggests that such neoepitopes are present in human skin and that their targeting by autoantibodies may contribute to disease pathogenesis.
Roh
J Y
JY
Dermatology Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Room 12N238, National Institutes of Health, 10 Center Drive MSC 1908, Bethesda, MD 20892-1908.
Yee
C
C
Lazarova
Z
Z
Hall
R P
RP
Yancey
K B
KB
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins; D003094:Collagen / Q000276:immunology*; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010390:Pemphigoid, Benign Mucous Membrane / Q000276:immunology*; D010391:Pemphigoid, Bullous / Q000276:immunology*; D011485:Protein Binding; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human