Tag Archives: desmoglein

Background.  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune vesicobullous disorders with IgG autoantibodies directed against desmoglein (Dsg)1 and 3, which lead to intraepidermal acantholysis.

Aim.  To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement.

Methods.  In total, 10 patients (7 women, 3 men; age range 24–70 years, disease duration 3–16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings .

Results.  Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24–266 in PF and 0–270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22–98) and was negative in all PF sera.

Conclusions.  All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical-cord region.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.2012.04468.x/abstract

Background  Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in patients with pemphigus.

Objectives  The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus.

Methods  IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay.

Results  Dsg-specific antibodies comprised a median of 7·1% and 4·2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with age-matched controls (P = 0·004 and P = 0·005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions.

Conclusions  Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2012.11144.x/abstract

Pemphigus vulgaris (PV) is an autoimmune disease in which the body’s immune system develops antibodies to two of its own proteins, the desmogleins DSG1 and DSG3 that help maintain the integrity of the skin. The immune attack causes painful blisters on the skin and mucus membranes that can lead to infections. Current therapies are geared towards suppressing the entire immune system, but this is problematic as it causes many side effects and leaves the patient vulnerable to infection.

To identify better therapeutic targets, researchers at the Institute for Research in Biomedicine in Bellinzona, Switzerland, identified the portions of DSG1 and DSG3 that are targeted by antibodies. In the study, published this month in the Journal of Clinical Investigation, Antonio Lanzavecchia and colleagues collected immune cells from PV patients and isolated the antibodies to determine which ones were involved in PV. By studying the antibodies, they were able to identify regions of DSG3 that are the primary target of the immune sysm. These findings could help with new ways to diagnose and treat PV.

Full article available at: http://www.medicalnewstoday.com/releases/249883.php


Various antigen-specific immunoassays are available for the serological diagnosis of autoimmune bullous diseases. However, a spectrum of different tissue-based and monovalent antigen-specific assays is required to establish the diagnosis. BIOCHIP mosaics consisting of different antigen substrates allow polyvalent immunofluorescence (IF) tests and provide antibody profiles in a single incubation.


Slides for indirect IF were prepared, containing BIOCHIPS with the following test substrates in each reaction field: monkey esophagus, primate salt-split skin, antigen dots of tetrameric BP180-NC16A as well as desmoglein 1-, desmoglein 3-, and BP230gC-expressing human HEK293 cells. This BIOCHIP mosaic was probed using a large panel of sera from patients with pemphigus vulgaris (PV, n equals 65), pemphigus foliaceus (PF, n equals 50), bullous pemphigoid (BP, n equals 42), and non-inflammatory skin diseases (n equals 97) as well as from healthy blood donors (n equals 100). Furthermore, to evaluate the usability in routine diagnostics, 454 consecutive sera from patients with suspected immunobullous disorders were prospectively analyzed in parallel using a) the IF BIOCHIP mosaic and b) a panel of single antibody assays as commonly used by specialized centers.


Using the BIOCHIP mosaic, sensitivities of the desmoglein 1-, desmoglein 3-, and NC16A-specific substrates were 90 percent, 98.5 percent and 100 percent, respectively. BP230 was recognized by 54 percent of the BP sera. Specificities ranged from 98.2 percent to 100 percent for all substrates. In the prospective study, a high agreement was found between the results obtained by the BIOCHIP mosaic and the single test panel for the diagnosis of BP, PV, PF, and sera without serum autoantibodies (Cohen’s kappa between 0.88 and 0.97).


The BIOCHIP mosaic contains sensitive and specific substrates for the indirect IF diagnosis of BP, PF, and PV. Its diagnostic accuracy is comparable with the conventional multi-step approach. The highly standardized and practical BIOCHIP mosaic will facilitate the serological diagnosis of autoimmune blistering diseases.

Full article available at: http://www.medworm.com/index.php?rid=6328120&cid=c_297_49_f&fid=36647&url=http%3A%2F%2Fwww.ojrd.com%2Fcontent%2F7%2F1%2F49