Serum Levels of Autoantibodies to BP180 Correlate With Disease Activity in Patients With Bullous Pemphigoid

Schmidt, Enno; Obe, Karin; Bröcker, Eva‐Bettina; Zillikens, Detlef

doi:10.1001/archderm.136.2.174

Cited by 313 publications

(295 citation statements)

References 33 publications

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“…An immunologic basis for BP was first suggested by the discovery of anti-BMZ Abs in patient sera and deposition of Igs and complement (C3) along the BMZ in biopsied skin (1). BP disease severity has been shown to be correlated with circulating levels of autoantibodies that recognize the epidermal protein, 180-kDa bullous pemphigoid Ag 2 (BP180, also termed type XVII collagen or BPAG2) (2)(3)(4)(5). Through the use of in vitro and in vivo models of BP, it has been established that BP180-specific autoantibodies are the primary pathogenic factors in this disease (6)(7)(8)(9).…”

mentioning

confidence: 99%

FcR-Independent Effects of IgE and IgG Autoantibodies in Bullous Pemphigoid

Messingham

Srikantha

DeGueme

et al. 2011

The Journal of Immunology

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Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgE and IgG class autoantibodies specific for 180-kDa BP Ag 2 (BP180), a protein involved in cell-substrate attachment. Although some direct effects of BP IgG have been observed on keratinocytes, no study to date has examined direct effects of BP IgE. In this study, we use primary cultures of human keratinocytes to demonstrate Ag-specific binding and internalization of BP IgE. Moreover, when BP IgE and BP IgG were compared, both isotypes stimulated FcR- independent production of IL-6 and IL-8, cytokines critical for BP pathology, and elicited changes in culture confluence and viability. We then used a human skin organ culture model to test the direct effects of these Abs on the skin, whereas excluding the immune inflammatory processes that are triggered by these Abs. In these experiments, physiologic concentrations of BP IgE and BP IgG exerted similar effects on human skin by stimulating IL-6 and IL-8 production and decreasing the number of hemidesmosomes localized at the basement membrane zone. We propose that the Ab-mediated loss of hemidesmosomes could weaken attachment of basal keratinocytes to the basement membrane zone of affected skin, thereby contributing to blister formation. In this article, we identify a novel role for IgE class autoantibodies in BP mediated through an interaction with BP180 on the keratinocyte surface. In addition, we provide evidence for an FcR-independent mechanism for both IgE and IgG class autoantibodies that could contribute to BP pathogenesis.

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confidence: 99%

FcR-Independent Effects of IgE and IgG Autoantibodies in Bullous Pemphigoid

Messingham

Srikantha

DeGueme

et al. 2011

The Journal of Immunology

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“…In fact, intracellular antigens such as BP230 or laminin have been described in BP or MMP, respectively (20). Consequently, the recombinant-proteinbased assay cannot at present be proposed as a satisfactory diagnostic laboratory tool, although anti-BP180 reactivity has been described as correlated to disease activity in previously described home-made EIAs (1,4,16). In conclusion, the new EIAs based on recombinant Dsg1 and Dsg3 can be used in the diagnosis of pemphigus and in the monitoring of disease, while the sensitivity of the EIA based on BP180 needs to be improved in order for it to be used in the diagnosis and monitoring of BP.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

D’Agosto

Latini

Carducci

et al. 2004

Clin Vaccine Immunol

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The diagnosis of autoimmune bullous diseases is based on clinical observation and on the presence of autoantibodies directed to molecules involved in the adhesion systems of the skin. Immunofluorescence assays are the currently accepted method for detection of autoantibodies; such assays depend greatly on the skill of operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1), Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. The present study was undertaken to evaluate the sensitivity and specificity of these immunoassays and to determine the correlation between the results and the clinical aspects of diseases. Serum samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from patients with unrelated autoimmune conditions were tested. Anti-desmoglein reactivity was detected in all the patients with pemphigus and in none of the controls. Patients with the more benign form of cutaneous disease had anti-Dsg1 antibodies, while patients with deeper cutaneous lesions or with mucosal involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay was positive for 66.6% of patients with bullous pemphigoid and for none of the patients with mucous membrane pemphigoid, and no reactivity was detected in the control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the diagnosis of pemphigus and provide information on the clinical phenotype of the disease. However, the sensitivity of EIA for detection of autoantibodies in bullous pemphigoid should be improved by the use of additional antigens or epitopes.Bullous autoimmune diseases are mediated by autoantibodies directed to the main adhesion systems of the skin (17). These diseases are classified into two major groups according to the level at which the skin blister occurs: pemphigus, characterized by epidermal blistering which is caused by loss of epidermal cell adhesion, and pemphigoid, characterized by subepidermal blistering which is caused by loss of adhesion between the basal keratinocytes and dermis (18). The detection of circulating or tissue-bound autoantibodies by immunofluorescence assay (IFA) is an important criterion for diagnosis in both clinical conditions (14). Recently, enzyme immunoassays (EIAs) based on recombinant desmoglein-1 (Dsg1) or Dsg3, the main autoantigens in pemphigus (1), and on recombinant BP180, the hemidesmosomal autoantigen involved in the pathogenesis of bullous pemphigoid (BP) (12, 19), have been commercialized. In the present study we have analyzed retrospectively the levels of anti-Dsg1 and anti-Dsg3 in the sera of patients with diagnoses of pemphigus and the levels of anti-BP180 in the sera of patients with pemphigoid in order to establish the correlation between the serum reactivity and clinical features of the patients. In fact, EIAs, compared to ...

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“…Memory B cells specific to this domain have been identified in BP patients [9]. The titer of anti-BP180 NC16A antibodies has repeatedly been shown to correlate with BP disease severity [10,11]. Additional antibodies outside the NC16 domain have also been detected in the sera of most BP patients [12].…”

Section: Bullous Pemphigoid (Bp)mentioning

confidence: 99%