BPAG2

Bullous pemphigoid (BP) is a common blistering disease caused by antibodies directed against hemi-desmosomal proteins BPAG1 and BPAG2. The disease is characterised by intense pruritus and blistering of the skin. The systemic treatment with the highest level of evidence for BP is systemic glucocorticoids. However, since the disease often occurs in the elderly patients, and since the most common co-morbidities are diabetes and neurological diseases, glucocorticoid-sparing drugs are often introduced. We retrospectively identified all BP patients admitted to our tertiary clinic over a 7-year period in order to register demography, treatment and co-morbidities...

Bullous pemphigoid (BP) is a common autoimmune blistering skin disorder that tends to affect the elderly. Autoantibodies (autoAbs) from BP patients react with two hemidesmosomal components: transmembrane collagen XVII (BP180 or BPAG2) and plakin family protein BP230 (BPAG1). Of these, collagen XVII (COL17) is thought to be a major autoantigen. The binding of autoAbs to COL17 following the activation of complements and inflammatory pathways eventually leads to the degradation of COL17, and this has been regarded as the main pathogenesis of BP...

Pemphigoid gestationis (PG), first described in 1872 by Laws Milton, is a rare autoimmune bullous disease of pregnancy and puerperium. Pemphigoid gestationis has been estimated to occur in 1: 50 000 pregnancies and usually presents in the second or third trimester with exacerbation after partum. This disease is caused by circulating IgG1 immunoglobulin against hemidesmosomal protein bullous pemphigoid BP180 (BPAG2) type XVII collagen and less frequently BP230. We present a case of pemphigoid gestationis in primigravida with complications during treatment due to the suspicion of pulmonary embolism...

Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell-extracellular matrix integrity...

α6β4 integrin is the main component of hemidesmosomes (HD) that stably anchor the epithelium to the underlying basement membrane. Epithelial cell migration requires HD remodelling, which can be promoted by epidermal growth factor (EGF). We previously showed that extracellular nucleotides inhibit growth factor-induced keratinocyte migration. Here, we investigate the effect of extracellular nucleotides on α6β4 integrin localisation in HD during EGF-induced cell migration. Using a combination of pharmacological inhibition and gene silencing approaches, we found that UTP activates the P2Y2 purinergic receptor and Gαq protein to inhibit EGF/ERK1/2-induced cell migration in keratinocytes...

Immune recognition and rejection of tissues expressing transfected genes is a major complication of gene replacement therapy for inherited genetic disorders. Owing to the high immunogenicity of human bullous pemphigoid antigen 2 (hBPAG2), the induction and maintenance of tolerance to this neo-antigen is essential to deliver the gene product to patients with epidermolysis bullosa junctionalis. In a skin grafting mouse model, we used gene gun transfection with a construct encoding hNC16A, the immunodominant domain of hBPAG2, to induce antigen-specific immune tolerance...

Bullous pemphigoid (BP) constitutes the most frequent autoimmune subepidermal blistering disease. It is associated with autoantibodies directed against the BP antigens 180 (BP180, BPAG2) and BP230 (BPAG1-e). The pathogenicity of anti-BP180 antibodies has been convincingly demonstrated in animal models. The clinical features of BP are extremely polymorphous. The diagnosis of BP critically relies on immunopathologic findings. The recent development of novel enzyme-linked immunosorbent assays has allowed the detection of circulating autoantibodies with relatively high sensitivity and specificity...

Pemphigoid (Pg) is an autoimmune subepidermal blistering disease that affects the elderly population. The phenotype can be Bullous Pemphigoid (BP), which primarily involves the skin, or Mucous Membrane Pemphigoid (MMP), which primarily involves mucus membranes. Ocular Cicatricial Pemphigoid (OCP) and Oral Pemphigoid (OP) are subsets of MMP. The known antigens in BP are Bullous Pemphigoid Antigen 1 (BPAG1, also known as BP230), Bullous Pemphigoid Antigen 2 (BPAG2, also known as BP180), and subunits of human integrins α6 and β4...

OBJECTIVE: To assess the usefulness of enzyme-linked immunosorbent assay (ELISA) assessment of the combination of bullous pemphigoid antigen 1 (BPAG1) and BPAG2 in the diagnosis of bullous pemphigoid (BP). DESIGN: Retrospective study of serum samples from patients with BP. SETTING: Tertiary care center. PATIENTS: A total of 190 patients with newly diagnosed BP and 78 controls with other autoimmune bullous diseases. INTERVENTION: Serum samples were tested using commercialized BPAG1 and BPAG2 ELISA and indirect immunofluorescence (IIF)...

In most stem cell systems, the organization of the stem cell niche and the anchoring matrix required for stem cell maintenance are largely unknown. We report here that collagen XVII (COL17A1/BP180/BPAG2), a hemidesmosomal transmembrane collagen, is highly expressed in hair follicle stem cells (HFSCs) and is required for the maintenance not only of HFSCs but also of melanocyte stem cells (MSCs), which do not express Col17a1 but directly adhere to HFSCs. Mice lacking Col17a1 show premature hair graying and hair loss...

Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis associated with pregnancy. Its previous designation, herpes gestationis, is obsolete. PG is characterized by a subepidermic separation induced by the presence of peripheral blood autoantibodies against two hemidesmosomal antigens: BPAG1 and BPAG2. Clinical diagnosis is confirmed by histology and positive cutaneous immunofluorescence tests. The most discriminant examination for other pruritic dermatoses of pregnancy is the enzyme-linked immunosorbent assay (Elisa) NC16A BP 180...

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP patients have autoantibodies against type XVII collagen (COL17, also called BP180 or BPAG2), a type II transmembrane protein that spans the lamina lucida and projects into the lamina densa of the epidermal basement membrane. The non-collagenous 16A domain of COL17 is considered to contain pathogenic epitopes of BP. The transfer of immunoglobulin (Ig)G from BP patients fails to cause blisters on mouse skin probably due to differences between humans and mice in the amino acid sequence of NC16A pathogenic epitope of COL17...

Several studies have suggested that autoantibodies directed against multiple epitopes occur via epitope spreading in autoimmune bullous skin diseases. However, the precise sequence of events in epitope spreading has not been elucidated for any of the epidermal autoantigens. In this issue, using a transgenic mouse model, Di Zenzo et al. report that intramolecular epitope spreading does occur for human BPAG2.

Bullous pemphigoid (BP) is a subepidermal autoimmune disease characterized by a humoral response to an epidermal basement membrane (BM) component, BP antigen 2 (BPAG2). BP patients have IgG autoantibodies against an immunodominant BPAG2 extracellular domain termed NC16A as well as additional epitopes located both in the intracellular and extracellular domains (ICD and ECD, respectively) of this autoantigen. To study the evolution of humoral responses to BPAG2, sequential serum samples obtained from C57BL/6Ncr mice grafted with otherwise syngeneic skin from transgenic mice expressing human BPAG2 (hBPAG2) in epidermal BM were studied for IgG reactivity to seven ECD and ICD hBPAG2 epitopes...

BACKGROUND: The 180-kDa transmembrane hemidesmosomal protein (BPAG2) has been identified as an important autoantigen in bullous pemphigoid (BP). Using the NC16A domain as the antigenic target, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of autoantibodies to BP180 was developed. AIM: To investigate the correlation of clinical severity and ELISA indices in BP. METHODS: Antibody titers in the sera from 20 patients were measured using BP180NC16a-ELISA, and an analysis of the correlation of ELISA indices with disease activity was performed...

A 7-year-old Caucasian girl had multiple bullae on the trunk, upper and lower limbs (Fig. 1a,b) for 10 days. The lesions were large, tense, and asymptomatic, and mucosae were not involved. Laboratory findings were all normal. Histopathology revealed a subepidermal blister containing numerous neutrophils, eosinophils, and fibrin. Direct immunofluorescence of perilesional skin disclosed linear deposition of IgA and slight linear deposits of IgM at the basement membrane zone (Fig. 2). Indirect immunofluorescence on monkey esophagus and on human salt-split skin was negative...

Bullous pemphigoid antigen 2 (BPAG2) is targeted by autoantibodies in patients with bullous pemphigoid (BP), and absent in patients with one type of epidermolysis bullosa (OMIM #226650). A keratin 14 promoter construct was used to produce transgenic (Tg) mice appropriately expressing human BPAG2 (hBPAG2) in murine epidermal basement membrane (BM). Grafts of Tg skin placed on gender-matched, syngeneic wild type (Wt) or major histocompatibility complex I (MHC I)-/- mice elicited IgG that bound human epidermal BM and BPAG2...

The protein bullous pemphigoid antigen-2 (BPAG2/BP180/collagen type XVII) plays a key role in attachment of basal keratinocytes to epidermal basement membrane. The binding of BP180 with either integrin alpha6, integrin beta4, or bullous pemphigoid antigen-1 (BPAG1/BP230) is critical for this attachment in skin. The protein 14-3-3 sigma, also known as stratifin and a marker for epithelial cells, is a member of a highly conserved small acidic 14-3-3 protein family naturally found in all eukaryotic cells. Here, we have used a 14-3-3sigma GST pull-down screening assay and showed that sigma (sigma) isoform of the 14-3-3 protein family interacts with the cytoplasmic N-terminal domain of BP180...

BACKGROUND: Bullous pemphigoid is an autoimmune disease, common in the elderly and generally of symmetrical and systemic localization. We report a case with sparing of the lower limb and acquired lymphedema secondary to lymph node surgery. CASE REPORT: A 74-year-old woman was hospitalized for a bullous eruption. The left lower limb was completely spared and was unaffected by pruritus. Acquired lymphedema was seen in this limb secondary to lymph node surgery. Standard histopathology tests confirmed the diagnosis of bullous pemphigoid with subepidermal blistering, while a direct immunofluorescence antibody test showed linear binding of IgG and C3 throughout the basement membrane...

Type XVII collagen, also referred to as bullous pemphigoid antigen 2 (BPAG2) or bullous pemphigoid antigen 180 (BP180), is a transmembrane protein of the hemidesmosomal complexes of keratinocytes. Type XVII collagen has an unusual type II orientation with its N-terminus intracellularly located and with a large extracellular domain that spans lamina lucida of the dermal-epidermal junction. Type XVII collagen is an autoantigen in patients with pemphigoid diseases and its gene is mutated in patients with junctional epidermolysis bullosa...