Wataru Nishie

Bullous pemphigoid (BP) is a common autoimmune skin disorder caused by autoantibodies targeting BP180. Recent evidence shows that dipeptidyl peptidase-4 inhibitors (DPP4i), used in diabetes management, can induce BP (DPP4i-BP). DPP4i-BP differs from typical BP in its genetic, clinical, and immunological features, but methods to specifically detect DPP4i-BP autoantibodies have been unavailable. This study used enzyme-linked immunosorbent assay with “domain-swapped BP180” proteins to identify autoantibodies in DPP4i-BP, which targeted BP180 regions from the seventh noncollagenous domain to the fourth collagenous domain (NC7-Col4). These epitopes were associated with DPP4i-BP–specific human leukocyte antigen class II peptide epitopes. Notably, the duration of DPP4i intake before BP onset was significantly shorter in patients with anti–NC7-Col4 autoantibodies than those without them. Measuring the autoantibodies enabled the early diagnosis of DPP4i-BP before epitope spreading. Furthermore, anti–NC7-Col4 autoantibodies were detected in some patients with diabetes taking DPP4i without BP, suggesting that these assays may offer potential tools for early identification of at-risk individuals.

Mucous membrane pemphigoid (MMP) is a mucous membrane‐dominated, subepidermal autoimmune blistering disease in which autoantibodies usually react with the C‐terminal domain of type XVII collagen (COL17) or with laminin‐332. Only a few cases of MMP with widespread blisters have been reported. Serologically, IgA and IgG class autoantibodies directed against COL17 or IgG autoantibodies directed against laminin‐332 in patients with MMP have been well documented. MMP cases in which IgA reacts with laminin‐332, however, are extremely rare. We report a case of MMP in a 67‐year‐old man. Clinical examination revealed extensive mucosal lesions as well as generalized blisters and erosions that healed with scar formation. The disease was intractable to treatment with systemic steroids. Interestingly, in addition to IgG directed against laminin‐332 and the noncollagenous 16A (NC16A) and C‐terminal domains of COL17, circulating IgA reacting with laminin‐332 and with the NC16A domain of COL17 was also detected. This is the first MMP case with circulating IgA and IgG autoantibodies against both laminin‐332 and COL17.