Increased Frequency of HLA-DR2 in Patients with Autoantibodies to Epidermolysis Bullosa Acquisita Antigen: Evidence that the Expression of Autoimmunity to Type VII Collagen Is HLA Class II Allele Associated

Gammon, W. Ray; Heise, Eugene R.; Burke, William A.; Fine, Jo‐David; Woodley, David T.; Briggaman, Robert A.

doi:10.1111/1523-1747.ep12470317

Cited by 148 publications

(58 citation statements)

References 30 publications

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“…Using timerestricted depletion of certain cell subsets, this new model was applied to investigate the cellular requirements for the early stages of EBA pathogenesis. Based on the findings presented in this article and elsewhere, we propose the following model of the early EBA pathogenesis: Both human (41,42) and experimental EBA (22) are strongly associated with certain MHC alleles. In addition, genes outside the MHC locus have recently been shown to influence susceptibility to experimental EBA (43).…”

Section: Discussionmentioning

confidence: 80%

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

Iwata

Bieber

Tiburzy

et al. 2013

The Journal of Immunology

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In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin or mucous membranes, or both. Mechanisms of continued autoantibody production and blistering have been well characterized using AIBD animal models. Mechanisms leading to the initial autoantibody production, however, have not been investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD associated with autoantibodies to type VII collagen (COL7). The majority of EBA patients’ sera recognize the noncollagenous domain 1, including the von Willebrand factor A–like domain 2 (vWFA2). In experimental EBA induced by immunization with GST-COL7, disease manifestation depended on the genetic background, a Th1 polarization, and the GST-tag. In this model, nude mice neither produced autoantibodies nor blisters. It has remained uncertain which APC and T cell subsets are required for EBA induction. We established a novel EBA model by immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse strains developed autoantibodies, but blisters were exclusively observed in mice carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected, and their induction required presence of B cells, dendritic cells, and macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the dermal side of salt-split skin and induced blisters when transferred into healthy mice. Absence of CD8 T cells at time of immunization had no effect, whereas depletion of CD4 T cells during the same time period delayed autoantibody production and blisters. Collectively, we demonstrate the pathogenic relevance of Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced CD4 T cells to induce experimental EBA.

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Section: Discussionmentioning

confidence: 80%

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

Iwata

Bieber

Tiburzy

et al. 2013

The Journal of Immunology

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“…14,15 There is no sex and racial predilection known, although several studies have reported an increased occurrence of the human leukocyte antigen (HLA)-DR2 allele in patients with EBA and bullous systemic lupus erythematosus (SLE). 16,17 This HLA phenotype has been associated with hyper-immunity which suggests an autoimmune etiology for EBA. The significance of certain HLA-DR2 molecules in the pathogenesis of EBA needs to be demonstrated in the context of specific autoantigens in future laboratory investigations.…”

Section: Introductionmentioning

confidence: 99%

“…The significance of certain HLA-DR2 molecules in the pathogenesis of EBA needs to be demonstrated in the context of specific autoantigens in future laboratory investigations. 16,17 Although EBA represents the rare autoimmune blistering disease in general, therapy for patients with EBA remains unsatisfactory, and mainly relies on immunosuppressive agents such as methotrexate, azathioprine or cyclophosphamide. [18][19][20][21] Thus, there is a need for the identification of safe and effective alternatives for treatment of EBA.…”

Section: Introductionmentioning

confidence: 99%

Epidermolysis bullosa acquisita: What’s new?

Ishii

Hamada

Dainichi

et al. 2010

The Journal of Dermatology

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Type VII collagen is an adhesion molecule of the extracellular matrix in epithelial basement membranes, and the main constituent of anchoring fibrils at the dermal-epidermal junction (DEJ). Autoimmunity against this protein is causing the rare organ-specific epidermolysis bullosa acquisita (EBA). EBA is a rare acquired, heterogeneous, chronic blistering disease of skin disease of skin and mucous membranes characterized by subepidermal blisters and tissue-bound as well as circulating autoantibodies to the DEJ. EBA has several distinct clinical presentations with other subepidermal bullous diseases, such as mainly dystrophic epidermolysis bullosa or bullous pemphigoid. The circulating immunoglobulin G autoantibodies for EBA react with a 290-kDa dermal protein, type VII collagen, as detected by immunoblot analysis using dermal extracts. The pathogenicity of these autoantibodies has been demonstrated by experimental animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA cases often require high doses of systemic corticosteroids and a variety of immunosuppressants. Although treatment for EBA is frequently difficult and unsatisfactory, some therapeutic success has been reported with colchicine, dapsone, infliximab and i.v. immunoglobulin. In this review, we will focus on recent progress in our understanding of the clinical manifestations, the etiopathogenesis as well as the management of EBA.

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“…3 There is association with allele HLA DR2, suggesting predisposition to EBA among carriers of this phenotype who are also more sensitive to bullous lupus. 4 The etiology is unknown although it is associated with the presence of antibodies against type VII collagen, main structural component of the anchorage fibrils of the dermo-epidermic junction, that could lead to a decrease in the number of anchorage fibrils. 2 The skin is fragile, bullae are formed spontaneously or usually after traumas.…”

Section: Introductionmentioning

confidence: 99%

Imunoglobulina intravenosa para tratamento de epidermólise bolhosa adquirida grave refratária a terapia imunossupressora convencional

Mosqueira

Furlani

Xavier

et al. 2010

An. Bras. Dermatol.

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Acquired bullous epidermolysis is a chronic and rare bullous subepidermal disease. It usually begins in adulthood and its etiology is unknown although it is associated with antibodies against type VII collagen. There are spontaneous and trauma induced formation of blisters that may cause serious complications. Treatment is disappointing and difficult. Apart from conventional therapy with systemic corticosteroid, new therapeutic modalities such as intravenous immunoglobulin are currently being used. This report highlights the extremely difficult clinical management of this rare disease and the important improvement provided by intravenous immunoglobulin. Keywords: Acquired bullous epidermolysis; Immunosuppressive agents; Immunoglobulins, intravenous Resumo: A epidermólise bolhosa adquirida é doença bolhosa subepidérmica crônica e rara. Geralmente, inicia-se na fase adulta, sendo a etiologia desconhecida, embora vinculada à presença de anticorpos contra o colágeno tipo VII. Há formação de bolhas, espontaneamente ou após trauma, podendo causar complicações graves. O tratamento é desapontador e difícil. Além da terapia convencional com corticoides sistêmi-cos, recentemente, novas modalidades terapêuticas promissoras estão sendo utilizadas, dentre elas, a imunoglobulina intravenosa. Destaca-se, neste relato, o difícil manejo clínico desta doença, e a melhora importante com a imunoglobulina intravenosa. Palavras-chave: Epidermólise bolhosa adquirida; Imunoglobulinas intravenosas; Imunossupressores

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Increased Frequency of HLA-DR2 in Patients with Autoantibodies to Epidermolysis Bullosa Acquisita Antigen: Evidence that the Expression of Autoimmunity to Type VII Collagen Is HLA Class II Allele Associated

Cited by 148 publications

References 30 publications

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

Epidermolysis bullosa acquisita: What’s new?

Imunoglobulina intravenosa para tratamento de epidermólise bolhosa adquirida grave refratária a terapia imunossupressora convencional

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