Clues to diagnosis for unusual mucosal pemphigus demonstrating undetectable anti-desmoglein 3 serum antibodies by routine tests.

Pemphigus is an autoimmune blistering disease caused by immunoglobulin (Ig)G autoantibodies against desmogleins (Dsg). In mucosal-dominant pemphigus vulgaris (PV), anti-Dsg3 antibodies play a critical role in acantholysis. We followed two mucosal-dominant PV cases who suffered from refractory oral mucosal erosions. In these cases, anti-Dsg3 serum antibodies were not detected by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA). However, direct immunofluorescence showed the intercellular IgG deposition in the epidermis and histopathological findings revealed suprabasal acantholysis. In order to analyze the pathomechanisms in these cases, we first examined the Dsg3 expression patterns in lesional sites and compared them with those of typical mucosal-dominant PV cases. In typical PV cases, the alteration of Dsg3 distribution was observed in lesional sites by immunostaining. The aggregation of Dsg3, which is the characteristic change in PV mucosal lesions, was observed as the initial change prior to acantholysis. In our cases, a clustering of Dsg3 was observed at mucosal lesions, and the expression levels of Dsg3 in acantholytic lesions were decreased, as observed in typical mucosal-dominant PV cases. Although anti-Dsg3 serum antibodies could not be detected by routine tests, anti-Dsg3 serum antibodies were detected by Dsg3 ELISA using 10-times more concentrated sera (highly sensitive ELISA). Moreover, purified and concentrated PV IgG showed high pathogenicity when examined by dissociation assay. In conclusion, the detection of morphological changes in Dsg3 distribution and highly sensitive ELISA method could be useful for the early diagnosis of PV recurrence.