IgG4 and IgE are the major immunoglobulins targeting the NC 16A domain of BP 180 in bullous pemphigoid: Serum levels of these immunoglobulins reflect disease activity

Döpp, Rebekka; Schmidt, Enno; Chimanovitch, Iakov; Leverkus, Martin; Bröcker, Eva‐B.; Zillikens, Detlef

doi:10.1016/s0190-9622(00)90168-3

Cited by 51 publications

(15 citation statements)

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“…Furthermore, anti-BP180-NC16A IgG subclasses were identical between healthy blood donors and BP patients (Table 3 ). Our result that no IgG4 anti-BP180-NC16A antibodies were detected in BP patients seemingly contradicts a previous report [ 33 ], although it might be due to the small number of BP serum samples included in our current study. In addition, the fine mapping of the autoantibody response in our samples revealed differences in the cohort of healthy blood donors compared to BP patients (Fig.…”

Section: Resultscontrasting

confidence: 99%

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Prüßmann

Koga

et al. 2015

Orphanet J Rare Dis

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BackgroundMucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results.MethodsTo clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF) microscopy using a biochip.ResultsCumulative prevalence of these autoantibodies was 0.9 % (CI: 0.7–1.1 %), with anti-BP180-NC16A IgG being most prevalent. Validation of IF findings using ELISA confirmed presence of autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and 2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid. Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals formed immune complexes with recombinant antigen and dose-dependently activated neutrophils in vitro. However, fine-epitope mapping within NC16A showed a different binding pattern of anti-BP180-NC16A autoantibodies from healthy individuals compared to bullous pemphigoid patients, while IgG subclasses were identical.ConclusionsCollectively, we here report a low prevalence of AIBD autoantibodies in a large cohort of healthy individuals. Furthermore, functional analysis shows differences between autoantibodies from healthy donors and AIBD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0278-x) contains supplementary material, which is available to authorized users.

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Section: Resultscontrasting

confidence: 99%

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Prüßmann

Koga

et al. 2015

Orphanet J Rare Dis

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“…Previously, we and others proposed a relationship between circulating total IgE [1], [37], [50], or BP180 specific IgE [37], [40], [51], [52], and the severity of clinical BP. Additionally, there is evidence for eosinophil degranulation in lesional tissue [22], [26] and, recently, we have shown that peripheral eosinophil numbers more accurately reflect disease activity than IgG autoantibody levels [53].…”

Section: Discussionmentioning

confidence: 99%

Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

et al. 2014

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Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE≥400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.

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“…Autoallergic mast cell activation has been implied to play a role in other chronic inflammatory skin disorders such as atopic dermatitis [17], [18] and bullous pemphigoid [19], [20], [21]. In both diseases IgE antibodies directed to skin antigens have been described and may play a role in the pathogenesis by activating cutaneous mast cells after binding their corresponding skin antigen.…”

Section: Discussionmentioning

confidence: 99%

IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?

et al. 2011

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BackgroundChronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.MethodsWe developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences.Principal FindingsCsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off ( = 5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPOlow ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86–5.44, = comparable to healthy controls) and 2) IgE-anti-TPOhigh ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.ConclusionOur findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.

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IgG4 and IgE are the major immunoglobulins targeting the NC 16A domain of BP 180 in bullous pemphigoid: Serum levels of these immunoglobulins reflect disease activity

Abstract: Our data demonstrate that remission of BP is paralleled by a decrease of serum levels of IgE and the different IgG subclasses reactive with BP180 NC16A.

Cited by 51 publications

References 35 publications

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Human Eosinophils Express the High Affinity IgE Receptor, FcεRI, in Bullous Pemphigoid

IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?

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