Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris

Mahoney, Mỹ G.; Wang, Zhihong; Rothenberger, Kyle; Koch, Peter J.; Amagai, Masayuki; Stanley, John R.

doi:10.1172/jci5252

Cited by 447 publications

(465 citation statements)

References 32 publications

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“…In patients with PV-associated skin or mucocutaneous lesions, both reactivities were present; only at the onset of disease did patients have single anti-Dsg3 reactivity, associated with mucous involvement. These features sustain the pathogenetic model described by Amagai, Stanley, and colleagues, based on the different distributions of Dsg1 and Dsg3 in skin or mucous epithelia (13). According to this model, based on the fact that Dsg1 is expressed in the entire epidermis and is minimally expressed in mucosal epithelia while Dsg3 expression is restricted to deeper epidermal layers and is widely expressed in mucosal epithelia, anti-Dsg1 autoantibodies should cause only skin lesions and affect the more superficial epidermal layers, since Dsg3 can compensate for the antibody-induced loss of Dsg1 function.…”

Section: Discussionsupporting

confidence: 73%

Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

D’Agosto

Latini

Carducci

et al. 2004

Clin Vaccine Immunol

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The diagnosis of autoimmune bullous diseases is based on clinical observation and on the presence of autoantibodies directed to molecules involved in the adhesion systems of the skin. Immunofluorescence assays are the currently accepted method for detection of autoantibodies; such assays depend greatly on the skill of operators and are difficult to standardize. Recombinant desmoglein-1 (Dsg1), Dsg3, and BP180 peptides, the main autoantigens in pemphigus or bullous pemphigoid, have been used to develop new quantitative enzyme immunoassays (EIA) for the detection of specific antibodies. The present study was undertaken to evaluate the sensitivity and specificity of these immunoassays and to determine the correlation between the results and the clinical aspects of diseases. Serum samples from patients with pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, or mucous membrane pemphigoid, from healthy individuals, and from patients with unrelated autoimmune conditions were tested. Anti-desmoglein reactivity was detected in all the patients with pemphigus and in none of the controls. Patients with the more benign form of cutaneous disease had anti-Dsg1 antibodies, while patients with deeper cutaneous lesions or with mucosal involvement had anti-Dsg3 reactivity also, or exclusively. The BP180-based assay was positive for 66.6% of patients with bullous pemphigoid and for none of the patients with mucous membrane pemphigoid, and no reactivity was detected in the control sera. In conclusion, the anti-Dsg1 and anti-Dsg3 assays are useful in the diagnosis of pemphigus and provide information on the clinical phenotype of the disease. However, the sensitivity of EIA for detection of autoantibodies in bullous pemphigoid should be improved by the use of additional antigens or epitopes.Bullous autoimmune diseases are mediated by autoantibodies directed to the main adhesion systems of the skin (17). These diseases are classified into two major groups according to the level at which the skin blister occurs: pemphigus, characterized by epidermal blistering which is caused by loss of epidermal cell adhesion, and pemphigoid, characterized by subepidermal blistering which is caused by loss of adhesion between the basal keratinocytes and dermis (18). The detection of circulating or tissue-bound autoantibodies by immunofluorescence assay (IFA) is an important criterion for diagnosis in both clinical conditions (14). Recently, enzyme immunoassays (EIAs) based on recombinant desmoglein-1 (Dsg1) or Dsg3, the main autoantigens in pemphigus (1), and on recombinant BP180, the hemidesmosomal autoantigen involved in the pathogenesis of bullous pemphigoid (BP) (12, 19), have been commercialized. In the present study we have analyzed retrospectively the levels of anti-Dsg1 and anti-Dsg3 in the sera of patients with diagnoses of pemphigus and the levels of anti-BP180 in the sera of patients with pemphigoid in order to establish the correlation between the serum reactivity and clinical features of the patients. In fact, EIAs, compared to ...

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Section: Discussionsupporting

confidence: 73%

Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

D’Agosto

Latini

Carducci

et al. 2004

Clin Vaccine Immunol

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“…Clinically, PV is a potentially life threatening autoimmune bullous disorder characterized primarily by mucosal lesions (generally when IgG autoAb against Dsg3 are present), and mucocutaneous blisters and erosions (when IgG autoAb against both Dsg3 and Dsg1 are present) (10,11). The titers of autoAb against Dsg3 and Dsg1 strongly correlate with activity of disease in individual patients (10,12).…”

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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“…4 Pemphigus is a group of rare and severe cutaneous organ-specific autoimmune diseases, characterized by the production of autoantibodies directed against desmosomal adhesion molecules expressed by keratinocytes 5 and responsible for the formation of intraepidermal blisters. In the sporadic form of pemphigus foliaceus (PF) and fogo selvagem, its endemic form observed in certain areas of Brazil, pathogenic autoantibodies bind to desmoglein 1 (DSG1), [6][7][8][9][10][11][12] a glycoprotein that mediates cell adhesion in the superficial layers of the epidermis. MHC class II loci have been demonstrated to participate in susceptibility to both forms of PF.…”

Section: Introductionmentioning

confidence: 99%

Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus

et al. 2002

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Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris

Cited by 447 publications

References 32 publications

Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

Evaluation of Recombinant Antigen-Based Assays for Diagnosis of Bullous Autoimmune Diseases

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

Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus

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