MABT118 Sigma-AldrichAnti-Desmoglein-1 Antibody, clone 32-2B

No tool is available to diagnose drug-induced pemphigus (DIP) and to predict its outcome after the withdrawal of the culprit drugs. This retrospective pemphigus case series study compared cutaneous/mucosal immunostaining of a monoclonal antibody directed toward desmogleins 1 and 3 (32-2B) in 37 patients with DIP and 56 patients with idiopathic pemphigus. There was a significant difference between the groups in terms of pruritus, superficial form, mucosal involvement, and circulating antibodies. 32-2B staining disclosed a patchy pattern in 47 (84%) of idiopathic pemphigus cases and in 11 (30%) of DIP cases (P<.0001). A normal pattern, used as a diagnostic test for DIP, had 70.3% sensitivity (95% confidence interval [CI], 53.0-84.1), 83.9% specificity (95% CI, 71.7-92.4), a 32.7% positive predictive value, and a 97.9% negative predictive value. Of 17 patients with DIP with a normal pattern of 32-2B, 14 recovered, whereas only 2 of 9 patients with DIP with a patchy pattern recovered (P<.005).32-2B immunolabeling is useful for diagnosing DIP and is an indicator of a good prognosis.

The epidermal blistering disease, pemphigus vulgaris (PV), is caused by circulating autoantibodies that react with a desmosomal glycoprotein desmoglein (Dsg3). This antigen is expressed only in stratified epithelial tissues. Here we show that the simple epithelial canine kidney cell line, MDCK, expresses at least two desmoglein isoforms recognised by different monoclonal antibodies. One of these isoforms is a 130 x 10(3) M(r) polypeptide that is recognised by both PV autoantisera and a monoclonal antibody reactive with a cytoplasmic domain of human Dsg3. Antibodies in PV sera bind to the surface of MDCK cells but not cause loss of intercellular adhesion. This is the first demonstration of the expression of a polypeptide related to human PV antigen by a simple epithelial cell type.

An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior.

A series of transitional cell carcinomas of bladder were stained immunohistochemically with the monoclonal antibody, 32-2B, to desmosomal glycoprotein 1. All of the sections showed positive staining with the antibody. Assessment of staining intensity, by 3 independent examiners, revealed a strong negative correlation between density of desmosomal staining and degree of invasion (P = 0.012). Nests of strongly staining cells were identified in several invasive tumours, possibly indicating early squamous differentiation. Invasive tumour cells in the subepithelial stroma also stained strongly with the antibody. Correlation with clinical course, however, revealed no significant association between desmosomal staining and the incidence of recurrence or progression. It is suggested that staining with this antibody may be of value in detecting both stromal invasion and early squamous differentiation of transitional cell carcinomas. Both this and previous studies emphasise the value of this antibody as an epithelial marker in neoplasia.

Desmosomes are intercellular adhesive junctions that occur in almost all epithelia and should therefore be useful as epithelial markers in tumour diagnosis. Here, we describe a monoclonal antibody, 32-2B, to a major desmosomal glycoprotein (dgl) which reacts with human tissues in paraffin sections. This antibody was tested for its ability to stain epithelia and tumours. It reacted with all epithelia tested and with every specimen of a wide range of carcinomas. It also stained meningiomas, another desmosome-containing tumour. It did not stain other types of tumours including lymphomas, melanomas, and various sarcomas, or normal tissues which lack desmosomes. These characteristics demonstrate that 32-2B is a reliable epithelial marker that may have a useful role in diagnostic histopathology.