Research Advances in Pemphigus

Anhalt, Grant J.; Díaz, Luis A.

doi:10.1001/jama.285.5.652

Cited by 49 publications

(16 citation statements)

References 32 publications

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“…Anti-epidermal autoantibodies, present in PV patient sera and easily detected by immunofluorescence (IF) on perilesional epidermis, are pathogenic; PV IgG reproduces the clinical, histologic, and immunologic features of the disease when passively transferred to neonatal mice. Pathogenic PV autoantibodies bind the dsg3 ectodomain in a calcium-dependent immunological reaction (6).…”

mentioning

confidence: 99%

Desmosome Signaling

Berkowitz¹,

Hu²,

Li³

et al. 2005

Journal of Biological Chemistry

215

113

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In the human autoimmune blistering disease pemphigus vulgaris (PV) pathogenic antibodies bind the desmosomal cadherin desmoglein-3 (dsg3), causing epidermal cell-cell detachment (acantholysis). Pathogenic PV dsg3 autoantibodies were used to initiate desmosome signaling in human keratinocyte cell cultures. Heat shock protein 27 (HSP27) and p38MAPK were identified as proteins rapidly phosphorylated in response to PV IgG. Inhibition of p38MAPK activity prevented PV IgG-induced HSP27 phosphorylation, keratin filament retraction, and actin reorganization. These observations suggest that PV IgG binding to dsg3 activates desmosomal signal transduction cascades leading to (i) p38MAPK and HSP27 phosphorylation and (ii) cytoskeletal reorganization, supporting a mechanistic role for signaling in PV IgG-induced acantholysis. Targeting desmosome signaling via inhibition of p38MAPK and HSP27 phosphorylation may provide novel treatments for PV and other desmosome-associated blistering diseases.

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mentioning

confidence: 99%

Desmosome Signaling

Berkowitz¹,

Hu²,

Li³

et al. 2005

Journal of Biological Chemistry

215

113

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“…These results again point to the idea that El Bagre EPF represents a novel variant of the disease. Nevertheless, the mechanism by which recognition of Dsg-1, and perhaps other antigens, contributes to the observed apoptosis [8, 9] and development of lesions in EPF is not known [1]. …”

Section: Immunologic Features Of El Bagre Epfmentioning

confidence: 99%

“…Most autoimmune diseases, including PV and PF, occur sporadically and are widely scattered geographically. However, endemic pemphigus foliaceus (EPF) represents an autoimmune disorder that is limited to a well-defined geographic area (reviewed in [1, 2]), such as Brazil or, as reviewed below, El Bagre, Columbia in South America [3]. This El Bagre EPF is also characterized by acantholytic skin lesions and by autoantibodies to Dsg-1 [3–5].…”

Section: Introductionmentioning

confidence: 99%

A Hypothesis Concerning a Potential Involvement of Ceramide in Apoptosis and Acantholysis Induced by Pemphigus Autoantibodies

Bollag

2010

Dermatology Research and Practice

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Autoimmune diseases affect more than 50 million Americans, resulting in significant healthcare costs. Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF) is an autoimmune skin disease localized to specific geographic loci. EPF, and the related diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are characterized by skin lesions and autoantibodies to molecules found on epidermal keratinocytes. A variant of EPF in patients from El Bagre, Colombia, South America, has recently been reported to be distinct from previously described loci in Brazil and Tunisia epidemiologically and immunologically. As in PF and EPF, El Bagre EPF patients exhibit autoantibodies towards desmoglein-1, a cell adhesion molecule critical for maintaining epidermal integrity. An association of El Bagre EPF with sun exposure has been detected, and ultraviolet irradiation also exacerbates symptoms in PV, PF and EPF. Our hypothesis is that: (1) the autoantibodies generate pathology through an alteration in ceramide metabolism in targeted keratinocytes, resulting in apoptosis and/or cell death and acantholysis, but only when the cell's ability to metabolize ceramide is exceeded, and (2) apoptosis in response to this altered ceramide metabolism is initiated and/or exacerbated by other agents that increase ceramide levels, such as cytokines, ultraviolet irradiation, and senescence.

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“…Clinically, PF affects only the skin, whereas PV initially affects mucous membranes (mucosal PV) and later involves the skin (mucocutaneous PV) [1, 3, 4]. The hallmark of all pemphigus phenotypes is the presence of intraepidermal vesicles [1] and anti-epidermal autoantibodies [2, 3, 5-7]. The anti-epidermal autoantibodies are detected bound to the surface of detached keratinocytes in lesional epidermis and circulating in the serum of patients [7].…”

Section: Introductionmentioning

confidence: 99%

“…The anti-epidermal autoantibodies are detected bound to the surface of detached keratinocytes in lesional epidermis and circulating in the serum of patients [7]. It has been well demonstrated that these anti-epidermal autoantibodies recognize desmogleins (Dsg), a family of desmosomal cell adhesion glycoproteins [1, 2, 5-7]. The desmosome is a cell-cell adhesion organelle present in keratinocytes and other squamous epithelial cells [8], and consists of core and plaque structural components.…”

Section: Introductionmentioning

confidence: 99%

Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease

Qian

Culton

Jeong

et al. 2016

Autoimmunity Reviews

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Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

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Research Advances in Pemphigus

Cited by 49 publications

References 32 publications

Desmosome Signaling

Desmosome Signaling

A Hypothesis Concerning a Potential Involvement of Ceramide in Apoptosis and Acantholysis Induced by Pemphigus Autoantibodies

Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease

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