053 Conformational epitope mapping of autoantibodies against BP180 in dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disorder caused by autoantibodies targeting BP180 and BP230. The major pathogenic epitope of BP non-collagenous 16th A (NC16A) domain BP180. However, often recognize non-NC16A epitopes, which include conformational epitopes BP180, within its triple-helical collagenous structure. Epidemiological studies have shown that dipeptidyl peptidase-4 inhibitor (DPP4i) anti-type II diabetes mellitus drugs are associated with an increased risk developing DPP4i-associated (DPP4i-BP) likely to target different than those conventional BP. These led us hypothesize may be involved in DPP4i-BP, though mapping strategies could not address this issue due linear structure recombinant protein. Herein we identify DPP4i-BP producing five constructs covering extracellular region were swapped into backbone collagen XIII (COL13), a transmembrane similar (designated as BP180s). We confirmed swapping BP180s can form trimer has epitope-retaining potential. then established ELISAs coated these proteins. BP180-swapped showed sera preferentially reacted 7 4 while did not. Our novel would effective innovative method efficiently detecting quantifying well distinguishing from based on autoantibody profiles.