Experimental bullous pemphigoid generated in mice with an antigenic epitope of the human hemidesmosomal protein BP230

Kiss, Mária; Husz, S.; Jánossy, Tamás; Marczinovits, Ilona; Molnár, J.; Korom, Irma; Dobozy, A.

doi:10.1016/j.jaut.2004.09.007

Cited by 69 publications

(57 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, in BP, the in situbound antibodies eluted from the lesional skin were found to be preferentially directed against BP230 [58]. Interestingly, Kiss et al reported more recently, in contrast to previous studies, an induction of subepidermal splits in neonatal mice injected with rabbit antibodies to BP230 [59]. This important finding suggests that the anti-BP230 antibodies do have access to their intracellular target antigen and further attests for a possible role of anti-BP230 antibodies in BP pathogenesis.…”

Section: Humoral Immune Response In Bullous Pemphigoidmentioning

confidence: 85%

The Pathophysiology of Bullous Pemphigoid

Kasperkiewicz

Zillikens

2007

Clinic Rev Allerg Immunol

162

155

View full text Add to dashboard Cite

Bullous pemphigoid (BP) is a blistering skin disease characterized by an autoimmune response to 2 hemidesmosomal proteins within the dermal-epidermal junction, designated BP180 and BP230. While BP230 localizes intracellularly and associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein with an extracellular domain. Most BP patients have autoantibodies binding to an immunodominant region of BP180, the noncollagenous 16A domain (NC16A), which is located extracellularly close to the transmembrane domain of the protein. Autoreactive T and B cell responses to BP180 have been found in patients with BP. Passive transfer of antibodies to the murine BP180 ectodomain triggers a blistering skin disease in mice that closely mimics human BP. Lesion formation in this animal model depends upon complement activation, mast cell degranulation and accumulation of neutrophils and eosinophils. Patients' autoantibodies to BP180 induce dermal-epidermal separation in cryosections of human skin when co-incubated with leukocytes. The loss of cell-matrix adhesion is mediated by proteinases released by granulocytes. The increased knowledge of the pathophysiology of BP should facilitate the development of novel therapeutic strategies for this disease.

show abstract

Section: Humoral Immune Response In Bullous Pemphigoidmentioning

confidence: 85%

The Pathophysiology of Bullous Pemphigoid

Kasperkiewicz

Zillikens

2007

Clinic Rev Allerg Immunol

162

155

View full text Add to dashboard Cite

show abstract

“…The blister-inducing capacity of Abs to various Ags, including desmosomal cadherins, acetylcholine receptors, type XVII collagen, laminin 5, BP230, and type VII collagen, has been characterized by passive transfer of (auto)antibodies into experimental animals (3)(4)(5)(6)(7)(8)(9)(10). By this approach, significant information has accumulated on the mechanisms effective in the skin that, after binding of autoantibodies, mediate blistering.…”

mentioning

confidence: 99%

Induction of Complement-Fixing Autoantibodies against Type VII Collagen Results in Subepidermal Blistering in Mice

Sitaru

Chiriac

Mihai

et al. 2006

The Journal of Immunology

141

194

View full text Add to dashboard Cite

Experimental models reproducing an autoimmune response resulting in skin blistering in immunocompetent animals are lacking. Epidermolysis bullosa acquisita (EBA) is a bullous skin disease caused by autoantibodies to type VII collagen. In this study, we describe an active disease model of EBA by immunizing mice of different strains with murine type VII collagen. All mice developed circulating IgG autoantibodies that recognized type VII collagen and bound to the lamina densa of the dermal-epidermal junction. Importantly, subepidermal blisters developed in 82% of SJL-1, 56% of BALB/c mice, and 45% of FcγRIIb-deficient mice, but not in SKH-1 mice. In susceptible animals, deposits of IgG1, IgG2, and complement C3 were detected at the dermal-epidermal junction. In contrast, in the nondiseased mice, tissue-bound autoantibodies were predominantly of the IgG1 subclass and complement activation was weak or absent. This active disease model reproduces in mice the clinical, histopathological, and immunopathological findings in EBA patients. This robust experimental system should greatly facilitate further studies on the pathogenesis of EBA and the development of novel immunomodulatory therapies for this and other autoimmune diseases.

show abstract

“…Several studies point to the pathogenicity of the antibodies directed against BPAG1. For example antibodies raised against human BPAG1 in rabbits cause blistering when injected into neonatal mice (Kiss et al, 2005). However, as BPAG1 is an intracellular protein it may be that in patients the antibodies against BPAG1 arise as a result, rather than a cause, of the disease; these antibodies may then enter damaged cells and amplify the response.…”

Section: Diseases Of Plectin and Bpag1mentioning

confidence: 99%

Plakin Proteins, Hemidesmosomes and Human Disease

Chidgey

2012

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

The plakin proteins are a family of cytolinker proteins that connect elements of the cell cytoskeleton to each other and to junctional complexes at the cell membrane. There are seven mammalian plakin proteins and they are characterised by the presence of a plakin domain and/or a plakin repeat domain. The plakins play a vital role in maintaining the integrity of tissues, such as the skin and heart, which are subjected to mechanical stress. Two plakin proteins, plectin and bullous pemphigoid antigen 1 (BPAG1), are essential components of hemidesmosomes, cell–extracellular matrix junctions of epithelial cells, and inherited mutations in either can result in the skin blistering disease epidermolysis bullosa simplex. Mutations in the desmosomal plakin protein desmoplakin can cause the heart muscle disorder arrhythmogenic right ventricular dysplasia, a common cause of sudden cardiac arrest and death in young adults. Plakin proteins are targeted by pathogenic autoantibodies in the skin blistering diseases bullous pemphigoid and paraneoplastic pemphigus. Key Concepts: The plakin proteins are a family of cytolinker proteins that connect elements of the cell cytoskeleton to each other and to junctional complexes at the cell membrane. Seven plakin proteins are found in mammals; plectin, BPAG1, desmoplakin, envoplakin, periplakin, microtubule–actin crosslinking factor 1 and epiplakin. Plectin and BPAG1 are important constituents of hemidesmosomes, cell–extracellular matrix junctions. Mutations in plakin proteins can result in skin blistering disease, muscular dystrophy, autonomic neuropathy and cardiomyopathy. Plakin proteins have been implicated in the autoimmune skin blistering diseases bullous pemphigoid and paraneoplastic pemphigus.

show abstract

Experimental bullous pemphigoid generated in mice with an antigenic epitope of the human hemidesmosomal protein BP230

Cited by 69 publications

References 35 publications

The Pathophysiology of Bullous Pemphigoid

The Pathophysiology of Bullous Pemphigoid

Induction of Complement-Fixing Autoantibodies against Type VII Collagen Results in Subepidermal Blistering in Mice

Plakin Proteins, Hemidesmosomes and Human Disease

Contact Info

Product

Resources

About