[New aspects on the pathogenesis of bullous pemphigoid].
Bullous pemphigoid (BP) is a subepidermal blistering autoimmune disease of the elderly. Autoantibodies are directed against two hemidesmosomal proteins, designated BP180 and BP230. While BP230 localizes intracellularly and associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein with an extracellular domain consisting of approximately 1000 amino acids. The non-collagenous (NC) 16A domain, that encompasses 76 amino acids and localizes directly adjacent to the transmembrane region, has been identified as an immunodominant region of the BP180 ectodomain. In the majority of BP sera, circulating antibodies to BP180 NC16A are detected; their serum levels correlate with disease activity. Neonatal mice that are injected with rabbit anti-murine BP180 antibodies develop a BP-like subepidermal blistering disease demonstrating the biological importance of antibodies to BP180. The pathogenically relevant site on murine BP180 corresponds to a stretch of the NC16A domain on human BP180. In contrast to pemphigus, in BP, autoantibodies alone are not sufficient to induce blisters. In addition, complement activation, the infiltration of inflammatory cells and the release of proteases and various inflammatory mediators, including cytokines, are essential for lesion formation. In this review, we give an up-date on the pathogenesis of BP.
Schmidt
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E
Universitäts-Hautklinik, Würzburg.
Bröcker
E B
EB
Zillikens
D
D
D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002352:Carrier Proteins; D003094:Collagen / Q000276:immunology*; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D012867:Skin / Q000276:immunology / Q000473:pathology; D000097805:Collagen Type XVII
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human; C095667:Dst protein, mouse