Super‐resolution imaging detects BP180 autoantigen in immunoglobulin M pemphigoid

Hirano, Yoko; Iwata, Hiroaki; Tsujuwaki, Masumi; Mai, Shoko; Mai, Yosuke; Imafuku, Kimiaki; Izumi, Kiyotaka; Koga, Hiroshi; Ujiie, Hideyuki

doi:10.1111/1346-8138.16260

Cited by 9 publications

(11 citation statements)

References 15 publications

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“…Patient #8 of our cohort showed a linear IgM deposition besides IgG and C3 at the DEJZ, which has been also described in up to 17% of BP patients investigated by Moriuchi et al (28,29). In a patient with exclusive IgM staining at DEJZ, detailed super-resolution imaging detected deposits close to the NC1 domain of collagen VII, suggesting once more that IgM antibodies possibly target the C-terminus of BP180 (28). Clinical manifestations included papules or urticarial lesions, without blisters or mucosal involvement.…”

Section: Discussionsupporting

confidence: 86%

“…Ex vivo complement fixation tests showed the inability of IgM autoantibodies to activate complement, which is considered to be the main pathogenetic mechanism in BP (27). Patient #8 of our cohort showed a linear IgM deposition besides IgG and C3 at the DEJZ, which has been also described in up to 17% of BP patients investigated by Moriuchi et al (28,29). In a patient with exclusive IgM staining at DEJZ, detailed super-resolution imaging detected deposits close to the NC1 domain of collagen VII, suggesting once more that IgM antibodies possibly target the C-terminus of BP180 (28).…”

Section: Discussionsupporting

confidence: 72%

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Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid—A Retrospective, Monocentric Study

et al. 2022

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Immune checkpoint inhibitors (ICI) induce T-cell-mediated antitumour responses. While ICI were initially successfully applied in metastasized melanoma, they are now approved for several tumour entities. Numerous autoimmune disorders have been reported to occur as adverse events of the treatment, among them bullous pemphigoid (BP), with less than 1% of the patients experiencing ICI-induced BP. This number is higher than the estimated prevalence of autoimmune bullous diseases in the general population of Germany, which lies around 0.05%. We here describe our cohort of eight patients, who developed a bullous pemphigoid under or shortly after ICI treatment. Half of them had a severe subtype (as shown by BPDAI >57) and showed a median onset of ICI-BP after 10 months of ICI initiation. Six patients had a palmar and/or plantar involvement, while oral involvement occurred in one case. All patients had linear epidermal IgG depositions in split skin in the indirect immunofluorescence. In four out of five biopsies available for direct immunofluorescence, linear IgG and C3 depositions were detected at the basement membrane, while one patient showed linear IgM staining. Moderate to high levels of FLBP180 autoantibodies were found in seven of eight cases. The disease can still be active after ICI discontinuation, while rituximab might be required for remission. Finally, four tumour samples were stained histochemically for collagen XVII (BP180), but no enhanced expression was found.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 72%

Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid—A Retrospective, Monocentric Study

et al. 2022

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“…In a systematic review of non-bullous pemphigoid described by Lamberts et al., the most common clinical presentations of patients with non-bullous pemphigoid were erythematous, urticarial plaques and papules/nodules, and 9.8% of the non-bullous pemphigoid patients developed bullae during the reported follow-up ( 63 ). In addition, an IgM autoantibody-mediated pemphigoid disease called IgM pemphigoid has been reported ( 95 – 97 ), and IgM autoantibodies targeting BP180 might play a pathogenic role in IgM pemphigoid ( 95 , 96 ). It is debatable whether non-bullous pemphigoid and IgM pemphigoid are just prodromes of BP or are distinct pemphigoid variants.…”

Section: Prodromal Bpmentioning

confidence: 99%

The significance of preclinical anti-BP180 autoantibodies

et al. 2022

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Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease. Although the pathomechanism of BP onset has yet to be elucidated in detail, BP autoantibodies targeting two hemidesmosomal components, BP180 and BP230, are known to play a pivotal role in BP pathogenesis. Thus, the detection and measurement of BP autoantibodies are necessary for diagnosing BP and monitoring the disease activity. Immune assays such as immunofluorescence microscopy, immunoblotting, and ELISAs using BP180 and BP230 detect BP autoantibodies in most BP cases with high specificity; however, BP autoantibodies are sometimes detected in BP patients before the onset of this disease. BP autoantibodies that are detected in patients without typical tense blisters are defined as “preclinical BP autoantibodies”. These preclinical BP autoantibodies are detected even in a low percentage of normal healthy individuals. Although the importance of preclinical BP autoantibodies remains elusive, these autoantibodies might be a potential risk factor for subsequent BP development. Therefore, previous comparative epidemiological studies have focused on the prevalence of preclinical BP autoantibodies in populations susceptible to BP (e.g., the elderly) or in diseases with a higher risk of comorbid BP. This mini-review summarizes the literature on the prevalence of preclinical BP autoantibodies in patients with various conditions and diseases, and we discuss the significance of preclinical BP autoantibody detection.

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“…IgE against these epitopes has also been detected ( 91 ). Recently, in patients without frank blistering but erythematosus lesions, exclusive IgM autoantibodies against BP180 have been reported ( 92 , 93 ). Boch et al.…”

Section: Epitopes On Bp180mentioning

confidence: 99%

Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

2022

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Pemphigoid diseases (PD) are autoimmune skin blistering diseases characterized by autoantibodies directed against proteins of the cutaneous basement membrane zone (BMZ). One of the major antigens is type XVII collagen (BP180), a transmembrane glycoprotein, which is targeted in four PDs: bullous pemphigoid, mucous membrane pemphigoid, linear IgA dermatosis, and pemphigoid gestationis. To date, different epitopes on BP180 have been described to be recognized by PD disease patients’ autoantibodies. Different BP180 epitopes were associated with distinct clinical phenotypes while the underlying mechanisms are not yet fully understood. So far, the main effects of anti-BP180 reactivity are mediated by Fcγ-receptors on immune cells. More precisely, the autoantibody–antigen interaction leads to activation of complement at the BMZ and infiltration of immune cells into the upper dermis and, by the release of specific enzymes and reactive oxygen species, to the degradation of BP180 and other BMZ components, finally manifesting as blisters and erosions. On the other hand, inflammatory responses independent of Fcγ-receptors have also been reported, including the release of proinflammatory cytokines and internalization and depletion of BP180. Autoantibodies against BP180 can also be found in patients with neurological diseases. The assumption that the clinical expression of PD depends on epitope specificity in addition to target antigens, autoantibody isotypes, and antibody glycosylation is supported by the observation that epitopes of PD patients differ from those of PD patients. The aim of the present review is to describe the fine specificities of anti-BP180 autoantibodies in different PDs and highlight the associated clinical differences. Furthermore, the direct effects after binding of the autoantibodies to their target are summarized.

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Super‐resolution imaging detects BP180 autoantigen in immunoglobulin M pemphigoid

Cited by 9 publications

References 15 publications

Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid—A Retrospective, Monocentric Study

Hemidesmosomal Reactivity and Treatment Recommendations in Immune Checkpoint Inhibitor-Induced Bullous Pemphigoid—A Retrospective, Monocentric Study

The significance of preclinical anti-BP180 autoantibodies

Type XVII collagen: Relevance of distinct epitopes, complement-independent effects, and association with neurological disorders in pemphigoid disorders

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