NBME Histology Practice Test

Autoantibodies in pemphigus vulgaris target desmosomes, the cell–cell adhesion junctions between keratinocytes in the epidermis (desmogleins are key components). When these junctions are attacked, keratinocytes lose their connections to each other, causing acantholysis and the formation of intraepidermal blisters just above the basal layer. This contrasts with diseases that target hemidesmosomes (anchoring cells to the basement membrane) and produce subepidermal blisters, or with disruptions of tight or gap junctions which don’t primarily cause acantholysis. Acantholysis is a hallmark feature, and clinically this often presents with a positive Nikolsky sign and mucosal involvement.