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Pemphigus vulgaris is primarily characterized by the presence of acantholysis, which is the process where keratinocytes lose their connections to each other, leading to the formation of blisters. This condition typically affects the epidermis and is often associated with Nikolsky's sign, where pressure on the skin can cause separation of the epidermis, resulting in blister formation.

In contrast, Mucous Membrane Pemphigoid is not associated with acantholysis but rather involves the subepithelial layer where the underlying dermis adheres to the epithelium. This condition is characterized by the presence of autoimmune antibodies against components of the basement membrane. The blister formation in Mucous Membrane Pemphigoid is due to separation at the level of the basement membrane and is generally less severe than in Pemphigus vulgaris.

Thus, the significant distinguishing feature between Pemphigus vulgaris and Mucous Membrane Pemphigoid is indeed the type of acantholysis. In Pemphigus vulgaris, acantholysis occurs within the epithelial layer, while in Mucous Membrane Pemphigoid, there is no acantholysis, since the interaction happens at the basement membrane level