Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion

Amagai, Masayuki; Klaus-Kovtun, Vera; Stanley, John R.

doi:10.1016/0092-8674(91)90360-b

Cited by 959 publications

(670 citation statements)

References 48 publications

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“…Pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceous (PF), is an autoimmune intraepidermal blistering diseases that target desmoglein 2 . Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that target BP180/NC16a 3 .…”

Section: Introductionmentioning

confidence: 99%

Antiphospholipid antibodies in patients with autoimmune blistering disease

Echigo

Hasegawa

Inaoki

et al. 2007

Journal of the American Academy of Dermatology

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Objective: To determine the serum levels and frequency of antiphospholipid antibodies (aPLs) and confirm the clinical importance of this antibodies in patients with autoimmune blistering disease (ABD). Methods:IgG and IgM anti-cardiolipin antibodies (aCL), IgG anti-cardiolipin-β 2 glycoprotein I complex antibody (aCL/β 2 GPI), and IgG anti-phosphatidylserine-prothrombin complex antibody (aPS/PT) were examined with an enzyme-linked immunosorbent assay in 71 patients with ABD, including pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid. Results:The prevalence of IgG aCL, IgM aCL, aCL/β 2 GPI, and IgG aPS/PT were positive for 22.4%, 9.1%, 9.9%, and 25.4% of the ABD patients, respectively, while they were not detected in any of the normal controls. Ten of 20 (50%) patients with ABD who were attending our hospital in 2004 were positive for aPLs, and thromboembolism was detected in 7/10 (70%) patients with aPLs.

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Section: Introductionmentioning

confidence: 99%

Antiphospholipid antibodies in patients with autoimmune blistering disease

Echigo

Hasegawa

Inaoki

et al. 2007

Journal of the American Academy of Dermatology

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“…is considered as a paradigm of an autoantibody (autoAb)-mediated autoimmune disease of the skin associated with a loss of epidermal cell-cell adhesion caused by autoAb against the desmosomal adhesion molecules, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) (1,2). The pathogenic role of Dsg-specific autoAb has been clearly established by different investigators in several in vitro and in vivo models (3)(4)(5).…”

Section: P Emphigus Vulgaris (Pv)mentioning

confidence: 99%

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Veldman¹,

Gebhard²,

Uter

et al. 2004

The Journal of Immunology

107

104

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Pemphigus vulgaris is a severe autoimmune disease caused by autoantibodies against the cutaneous adhesion molecule, desmoglein 3 (Dsg3). The aim of this study was to characterize the specificity of autoreactive Th cells, which presumably regulate Dsg3-specific autoantibody production. Ninety-seven Th1 and Th2 clones isolated from 16 pemphigus patients and 12 HLA-matched healthy donors recognized the Dsg3 peptides, DG3(78-94), DG3(96-112), DG3(189-205), DG3(205-221), and DG3(250-266). Peptide DG3(96-112), and to a lesser extent DG3(250-266), was recognized by the majority of T cells from patients and healthy donors in association with HLA-DRB1*0402 and DQB1*0503 which were prevalent in the pemphigus patients and Dsg3-responsive healthy donors. Analyzing the Vβ-chain of the TCR of the DG3(96-112)-specific T cells showed no restricted TCR usage. Peptides DG3(342-358) and DG3(376-392) were exclusively recognized by T cell clones (n = 13) from patients while DG3(483-499) was only recognized by T cell clones (n = 3) from a healthy donor. All Dsg3 peptides contained conserved amino acids at relative positions 1, 4, and 6; amino acids with a positive charge at position 4 presumably represent anchor motifs for DRB1*0402. These findings demonstrate that T cell recognition of distinct Dsg3 peptides is restricted by distinct HLA class II molecules and is independent from the development of pemphigus vulgaris.

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“…Several clinical variants of pemphigus have been identified based on the clinical phenotype and distinct autoAb profiles (2). Pemphigus vulgaris (PV) is caused by autoAb against the extracellular domain (ECD) of desmoglein 3 (Dsg3), while pemphigus foliaceus, a clinically less severe disorder, is caused by autoAb against the ECD of Dsg1 (1,3). AutoAb production in PV is polyclonal, and most autoAb are of the IgG4 subclass in pemphigus patients with active disease (4), while patients with chronic disease have autoAb of the IgG1 and IgG4 subtypes, and healthy relatives of PV patients and healthy carriers of PV-prevalent HLA class II alleles appear to have low levels of Dsg3-reactive IgG1 (4,5).…”

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confidence: 99%

Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

Veldman

Stauber²,

Waßmuth³

et al. 2003

The Journal of Immunology

115

121

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Pemphigus vulgaris (PV) is the most severe autoimmune bullous skin disorder and is primarily associated with circulating autoantibodies (autoAb) against desmoglein 3 (Dsg3). In light of recent evidence that autoreactive T cells are critical for the induction and regulation of Ab production, the goal of this study was to characterize and quantitate autoreactive T cells in patients with PV and healthy controls. Peripheral Dsg3-reactive Th cells from 28 patients with acute-onset, chronic active, and remittent PV were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all studied PV patients, while the number of autoreactive Th1 cells exceeded those of Th2 cells in chronic active PV. In contrast, healthy carriers of the PV-associated HLA class II alleles, DRB1*0402 and DQB1*0503, exhibited exclusively Dsg3-reactive Th1 cell responses, while healthy carriers of other HLA class II alleles did not. Moreover, the presence of IgG1 and IgG4 against Dsg3 was directly related to the ratio of Dsg3-reactive Th1/Th2 cells. T cell recognition of Dsg3 was restricted by HLA-DRB1*0402 and DQB1*0503 in PV patients and Dsg3-responsive healthy donors. These observations strongly suggest 1) that the appearance of Dsg3-reactive Th2 cells is restricted to patients with PV; 2) that specific HLA class II alleles that are prevalent in PV are critical for T cell recognition of Dsg3 in PV patients and Dsg3-responsive healthy donors; and 3) that autoAb production is associated with both Th1 and Th2 cells.

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Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion

Cited by 959 publications

References 48 publications

Antiphospholipid antibodies in patients with autoimmune blistering disease

Antiphospholipid antibodies in patients with autoimmune blistering disease

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

Dichotomy of Autoreactive Th1 and Th2 Cell Responses to Desmoglein 3 in Patients with Pemphigus Vulgaris (PV) and Healthy Carriers of PV-Associated HLA Class II Alleles

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