Distinctive Reactivity to the C-terminal Epitope of BP180 Characterizes Immune Checkpoint Inhibitor–associated Bullous Pemphigoid, and an ELISA Based on the BP180 Ectodomain Enables Prompt Diagnosis in a Subset of Patients
Year: 2026
Type: article
Study design: Observational Study
Abstract: Growing evidence has linked bullous pemphigoid (BP) to immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, the immunological features of ICI-associated BP (ICI-BP) are not yet fully elucidated. In order to characterize the humoral response in ICI BP patients and investigate whether their epitope profile differs from idiopathic BP (IBP), 53 ICI-BP patients were enrolled, immunologically characterized and compared with 59 IBP patients. ICI-BP had a distinctive IgG humoral profile, with reduced reactivity toward BP230 and recognition of multiple BP180 epitopes beyond the immunodominant extracellular noncollagenous 16A domain (NC16A). Specifically, reactivity to BP180 ectodomain was present in 94% of ICI-BP and 78% of IBP (p=0.044). Moreover, BP180 C-terminal epitope was more frequently targeted in ICI-BP than IBP (72% vs 41%, p=0.002). Notably, the combined use of an in-house BP180 ectodomain ELISA and the commercial BP180 test increased diagnostic sensitivity from 83% to 100%. Enhanced IgG reactivity toward nonimmunodominant epitopes, and especially C-terminal epitope recognition, characterize the humoral immune response in ICI-BP. Our data suggest that combining NC16A and fulllength BP180 ectodomain ELISAs may help reduce diagnostic delay in ICI-BP patients, in whom a timely diagnosis is crucial to appropriately manage the disease and ultimately avoid discontinuation of cancer therapy.
Source: Acta Dermato Venereologica
Authors: Anna Pira, Martina Merli, Feliciana Mariotti, Marco Andreani, Angelo Valerio Marzano, Clara De Simone, Rosa Falcone, Giuseppe Testa, Battarra Mariarosa, Maurizio Romagnuolo, Pietro Sollena, Federica De Galitiis, Emiliano Antiga, Roberto Maglie, Dario Didona, Jo Linda Maria Sinagra, Marzia Caproni, Michael Hertl, Emanuele Cozzani, Pamela Vezzoli, Laura Calabrese, Giovanni Paolino, Sofia Verkhovskaia, Luca Fania, Giulia Gasparini, Anna Rita Giampetruzzi, Biagio Didona, Pietro Quaglino, Giovanni Di Zenzo
Institutions: Istituto Dermopatico dell'Immacolata, A. O. Ordine Mauriziano di Torino, University of Turin, Bambino Gesù Children's Hospital, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, University of Siena, University of Florence, Philipps University of Marburg, Ospedale Policlinico San Martino, University of Genoa, Ospedale Papa Giovanni XXIII, IRCCS Ospedale San Raffaele
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,725
OpenAlex ID: W7166660949