Missing the target: Characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay

Fairley, Janet A.; Bream, Matthew J.; Fullenkamp, Colleen; Syrbu, Sergei; Chen, Mei; Messingham, Kelly A. N.

doi:10.1016/j.jaad.2012.09.012

Cited by 45 publications

(77 citation statements)

References 39 publications

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“…BP patients with IgG reactivity to regions of BP180 outside the immunodominant NC16A region [44] were not included in this study. Circulating eosinophil counts were also obtained for most BP patients.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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“…Use of the BP230 ELISA in the above study would only have detected 1 of the 4 patients with non-NC16A BP [12]. …”

Section: Resultsmentioning

confidence: 99%

Association of Autoantibodies to BP180 with Disease Activity in Greek Patients with Bullous Pemphigoid

Patsatsi

Kyriakou

Pavlitou-Tsiontsi

et al. 2012

Clinical and Developmental Immunology

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39 bullous pemphigoid (BP) patients were studied to assess the clinical significance of anti-BP180 and anti-BP230 circulating autoantibodies of BP and correlate their titers with the clinical scores of the BP Disease Area Index (BPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) as well as with the intensity of pruritus measured by the BPDAI pruritus component. All parameters were evaluated by the time of diagnosis (baseline), month 3, and month 6. Titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (r = 0.557, P value < 0.0001) and ABSIS (r = 0.570, P value < 0.0001) values, as well as with BPDAI component for the intensity of pruritus (rho = 0.530, P value = 0.001) at baseline. At month 3, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (rho = 0.626, P value = 0.000) and ABSIS (rho = 0.625, P value = 0.000) values, as well as with the BPDAI component for the intensity of pruritus (rho = 0.625, P value = 0.000). At month 6, titers of anti-BP180 autoantibodies were strongly correlated with BPDAI (rho = 0.527, P value = 0.001) and ABSIS (rho = 0.526, P value = 0.001) values, as well as with the BPDAI component for the intensity of pruritus (rho = 0.525, P value = 0.001). There was no statistically significant correlation between titers of anti-BP230 autoantibodies and the BPDAI, ABSIS, and BPDAI component for the intensity of pruritus at the same time points.

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“…[25,45,[95][96][97] Epitopes outside the NC16A domain have also been described to be recognized by IgE. [46,97,98] BP180 peptides were detected on mast cells and basophils from BP patients with IgE autoantibodies against NC16A and both cell types degranulated upon exposure to recombinant NC16A. [45] Furthermore, IgE-coated mast cells were detected in perilesional skin of BP patients.…”

Section: Bp180-specific Ige Autoantibodiesmentioning

confidence: 99%

IgE-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases

Beek

Schulze

Zillikens

et al. 2015

Expert Review of Clinical Immunology

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Autoimmune bullous diseases (AIBDs) are characterized by autoantibodies against structural proteins of the dermal-epidermal junction (in pemphigoid diseases) and the epidermal/ epithelial desmosomes (in pemphigus diseases). By far, the most common AIBD is bullous pemphigoid, which is immunopathologically characterized by autoantibodies against BP180 (type XVII collagen) and BP230. IgG and, to a lesser extent, IgA autoantibodies are the major autoantibody isotypes in these disorders. IgE autoantibodies are increasingly reported in particular in bullous pemphigoid. The development of specific and sensitive anti-BP180 IgE ELISA systems, the report of two experimental murine models employing IgE autoantibodies against BP180, and the successful treatment of bullous pemphigoid with the anti-IgE antibody omalizumab have raised interest in the role of IgE autoantibodies and the modulation of their production in AIBDs. Here, the relevance of IgE autoantibodies in the diagnosis, pathophysiology, and treatment decisions of AIBDs, with a focus on bullous pemphigoid, is reviewed. ARTICLE HISTORY

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Missing the target: Characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay

Cited by 45 publications

References 39 publications

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

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

Association of Autoantibodies to BP180 with Disease Activity in Greek Patients with Bullous Pemphigoid

IgE-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases

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