The gold standard for the diagnosis of pemphigus vulgaris is the detection of autoantibodies or complement component 3 by direct immunofluorescence microscopy of a perilesional biopsy.
This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1alpha and TNF-alpha.
T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRbeta1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRbeta1*0402, and by HLA-DQbeta1*0301.
We demonstrate that Pkp3 becomes tyrosine phosphorylated as early as 30 min upon binding of PV IgG to keratinocyte surface and eventually detaches from its binding partner desmoglein 3 (Dsg3).
Sera from patients with PV contained significantly greater levels of anti-Dsg3 autoantibodies than walnut-specific antibodies, suggesting that the autoreactive B-cell response in patients with PV might be initially triggered by walnut antigens but is subsequently driven by Dsg3.
We provide evidence that both pemphigus foliaceus-IgG containing Dsg 1- but not Dsg 3-specific antibodies and pemphigus vulgaris-IgG with antibodies to Dsg 1 and Dsg 3 were equally effective in causing epidermal splitting in human skin and keratinocyte dissociation in vitro.
Pemphigus vulgaris is a rare chronic blistering skin disease resulting from IgG autoantibodies directed against transmembrane desmosomal glycoprotein desmoglein 3 and is the most common form of pemphigus.
In this study, the genes for two autoantigens (DSG1 for pemphigus foliaceus and DSG3 for pemphigus vulgaris) were mapped on band q12 of human chromosome 18 by fluorescence in situ hybridization.
These observations allow us to propose a concept for pemphigus blistering disorders as a "desmosome-remodeling impairment disease" involving a mechanism of Dsg3 nonassembly and depletion from desmosomes through PV immunoglobulin G-activated intracellular signaling events.
Pemphigus vulgaris (PV) is an autoimmune blistering disease, in which autoantibodies against PV antigen (PVA or Dsg3) play a pathogenic role in inducing blister formation.
It was assumed that PV is caused by anti-desmoglein (Dsg) 3 autoimmunity because absorption of PV sera with a chimeric baculoprotein containing the Dsg 3 and IgG1 portions, rDsg3-Ig-His, eliminated disease-causing antibodies.
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.
The mucosal blister-producing PV variant is characterized by autoantibodies against desmoglein (Dsg)3, whereas mucosal and skin lesion-producing PV is characterized by autoantibodies to Dsg3 and Dsg1.
The diagnosis of neonatal pemphigus was made after the neonate and mother were found to have elevated desmoglein 3 (Dsg3) antibodies in conjunction with histopathologic features of pemphigus vulgaris.
To define cut-off values for Dsg1, Dsg3, and BP180, we evaluated 47 serum samples from patients with pemphigus foliaceus (PF), 59 from those with pemphigus vulgaris (PV), 52 from those with bullous pemphigoid (BP), and 995 from healthy individuals.
Specific Human Leukocyte Antigen Class II (HLA II) molecules associated with pemphigus vulgaris (PV), mucous membraine pemphigoid (MMP), and mixed connective tissue disease (MCTD) may react with multiple T cell epitopes within desmoglein 3 (Dsg 3), bullous pemphigoid antigen 2 (BPAG 2), and 70 kDa polypeptide small nuclear ribonucleoproteins (snRNP70) in autoantibody production.
Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner.