Glucocorticoids: The mode of action in bullous pemphigoid

Kubin, Minna E.; Hellberg, Lars; Palatsi, Riitta

doi:10.1111/exd.13408

Cited by 9 publications

(6 citation statements)

References 116 publications

(175 reference statements)

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“…Bullous pemphigoid (BP) is a skin-specific autoimmune disease characterized by subepidermal blisters (1–4). Systemic glucocorticoids and immunosuppressive agents are effective treatment options for BP (5, 6), but they increase the risk of lethal infections, particularly in elderly patients (7, 8). The autoimmune mechanisms involved in BP have been well-discussed based on clinical and experiential evidence (9, 10).…”

Section: Introductionmentioning

confidence: 99%

Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Tie

Natsuga

et al. 2019

Front. Immunol.

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Bullous pemphigoid (BP) is an autoimmune disease characterized by the formation of blisters, in which autoantibodies mainly target type XVII collagen (ColXVII) expressed in basal keratinocytes. BP IgG is known to induce the internalization of ColXVII from the plasma membrane of keratinocytes through macropinocytosis. However, the cellular dynamics following ColXVII internalization have not been completely elucidated. BP IgG exerts a precise effect on cultured keratinocytes, and the morphological/functional changes in BP IgG-stimulated cells lead to the subepidermal blistering associated with BP pathogenesis. Based on the electron microscopy examination, BP IgG-stimulated cells exhibit alterations in the cell membrane structure and the accumulation of intracellular vesicles. These morphological changes in the BP IgG-stimulated cells are accompanied by dysfunctional mitochondria, increased production of reactive oxygen species, increased motility, and detachment. BP IgG triggers the cascade leading to metabolic impairments and stimulates cell migration in the treated keratinocytes. These cellular alterations are reversed by pharmacological inhibitors of Rac1 or the proteasome pathway, suggesting that Rac1 and proteasome activation are involved in the effects of BP IgG on cultured keratinocytes. Our study highlights the role of keratinocyte kinetics in the direct functions of IgG in patients with BP.

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Section: Introductionmentioning

confidence: 99%

Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Tie

Natsuga

et al. 2019

Front. Immunol.

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“…In our study, we detected Th17 cell responses against BP180 in a few patients with BP and only to a minor extent in EP with pruritic disorders. The role of IL-17-producing T cells in BP has been partially elucidated (30,(42)(43)(44)(45)(46). Recently, it was shown that mRNA levels of IL-17 were upregulated in perilesional skin of BP patients (30,46) and inhibition of IL-17 with anti-IL-17 antibodies prevents BP180 IgG-induced blister formation (30,46).…”

Section: Discussionmentioning

confidence: 99%

Autoreactive Peripheral Blood T Helper Cell Responses in Bullous Pemphigoid and Elderly Patients With Pruritic Disorders

et al. 2021

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Bullous pemphigoid (BP) is a prototypic autoimmune disorder of the elderly, characterized by serum IgG autoantibodies, namely anti-BP180 and anti-BP230, directed against components of the basal membrane zone that lead to sub-epidermal loss of adhesion. Pruritus may be indicative of a pre-clinical stage of BP, since a subset of these patients shows serum IgG autoantibodies against BP230 and/or BP180 while chronic pruritus is increasingly common in the elderly population and is associated with a variety of dermatoses. Clinical and experimental evidence further suggests that pruritus of the elderly may be linked to autoimmunity with loss of self-tolerance against cutaneous autoantigens. Thus, the objective of this study was to determine autoreactive T cell responses against BP180 in elderly patients in comparison to patients with BP. A total of 22 elderly patients with pruritic disorders, 34 patients with bullous or non-bullous BP and 34 age-matched healthy controls were included in this study. The level of anti-BP180 and anti-BP230 IgG serum autoantibodies, Bullous Pemphigoid Disease Area Index (BPDAI), and pruritus severity were assessed for all patients and controls. For characterization of the autoreactive T cell response, peripheral blood mononuclear cells were stimulated ex vivo with recombinant BP180 proteins (NH2- and COOH-terminal domains) and the frequencies of BP180-specific T cells producing interferon-γ, interleukin (IL)-5 or IL-17 were subsequently determined by ELISpot assay. Patients with BP showed a mixed Th1/Th2 response against BP180 while autoreactive Th1 cells were identified in a minor subset of elderly patients with pruritic disorders. Furthermore, our T cell characterization revealed that therapeutic application of topical clobetasol propionate ointment in BP patients significantly reduced peripheral blood BP180-specific T cells, along with clinically improved symptoms, strongly suggesting a systemic immunosuppressive effect of this treatment.

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“…23,43 However, the refractory nature of some patients to corticosteroids merits further study. 44,45…”

Section: Bullous Pemphigoidmentioning

confidence: 99%

Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

Santi

Gripp

Roselino

et al. 2019

An. Bras. Dermatol.

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Bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases whose antigenic target is located at the basement membrane zone. Mucous membrane pemphigoid and epidermolysis bullosa acquisita can evolve with cicatricial mucosal involvement, leading to respiratory, ocular and/or digestive sequelae with important morbidity. For each of these dermatoses, a literature review covering all therapeutic options was performed. A flowchart, based on the experience and joint discussion among the authors of this consensus, was constructed to provide treatment orientation for these diseases in Brazil. In summary, in the localized, low-risk or non-severe forms, drugs that have immunomodulatory action such as dapsone, doxycycline among others may be a therapeutic option. Topical treatment with corticosteroids or immunomodulators may also be used. Systemic corticosteroid therapy continues to be the treatment of choice for severe forms, especially those involving ocular, laryngeal-pharyngeal and/or esophageal mucosal involvement, as may occur in mucous membrane pemphigoid and epidermolysis bullosa acquisita. Several immunosuppressants are used as adjuvant alternatives. In severe and recalcitrant cases, intravenous immunoglobulin is an alternative that, while expensive, may be used. Immunobiological drugs such as rituximab are promising drugs in this area. Omalizumab has been used in bullous pemphigoid.

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Glucocorticoids: The mode of action in bullous pemphigoid

Cited by 9 publications

References 116 publications

Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Autoreactive Peripheral Blood T Helper Cell Responses in Bullous Pemphigoid and Elderly Patients With Pruritic Disorders

Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

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