Although the analysis of skin BPDAI highlighted an increase in the blisters/erosions activity in BP patients with mucosal involvement, serum titers of autoantibodies directed against BP180-NC16A, the dominant autoantigen in BP, were not different between patients with and without mucosal involvement. Of note, Hofmann et al. showed that the presence of autoantibodies against both the BP180 N- and C-terminal of the ectodomain was associated with the presence of mucosal lesions (44). Then, Di Zenzo et al. (21) and Mariotti et al. (45) found that autoantibody reactivity against three extracellular epitopes of BP180 (NC16A, AA 1,080–1,107 and AA 1,331–1,404) appeared to be related to the presence of both skin and mucosal involvement in BP patients. By contrast, in our study, the uni- and multivariate analysis highlighted that the absence of anti-BP230 antibody was the only factor independently associated with mucosal involvement in BP. This unconventional result could imply that the immune response may be shifted toward other autoantibodies in those BP patients with mucosal involvement which could be related to a lower threshold of tolerance breakdown in line with a reduced level of Treg cells or of Treg homing as mentioned above. Based on a recent publication (20), we can hypothesize that the loss of immune tolerance curbs both the innate and the adaptive immune responses, which leads to the release of a specific panel of proteases associated with blister formation and tissue remodeling, and subsequently to a shift of the epitope targeted as compared with the classical pathophysiological mechanisms associated with BP. Altogether, this could be reflected by a reduced activity of the adaptive immune response toward the hemidesmosomal proteins of the basal keratinocyte layer and an increased activity toward the antigenic cryptic domains of molecules involved in the anchoring of those basal keratinocyte to the basal membrane structure. To address those mechanisms, it would be relevant to compare in future prospective studies the number and the activity of Treg in biopsy specimens from either skin or mucosa BP lesions with others samples collected from patients with inflammatory non-autoimmune diseases.