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

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.

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Publication Details

Journal
Acta Dermato Venereologica
Published
2026-06-29
DOI
https://doi.org/10.2340/actadv.v106.adv-2026-0336
Primary Topic
Autoimmune Bullous Skin Diseases
Type
article
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article

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

Pamela Vezzoli, Marco Andreani, Angelo Valerio Marzano, Jo Linda Sinagra et al.
Acta Dermato Venereologica
Autoimmune Bullous Skin Diseases
article

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

Pamela Vezzoli, Marco Andreani, Angelo Valerio Marzano, Jo Linda Sinagra, Giovanni Paolino, Anna Rita Giampetruzzi, Biagio Didona, Anna Pira, Emanuele Cozzani, Martina Merli, Laura Calabrese, Mariarosa Battarra, Giulia Gasparini, Emiliano Antiga, Feliciana Mariotti, Michael Hertl, Marzia Caproni, Maurizio Romagnuolo, Roberto Maglie, Federica De Galitiis, Dario Didona, Pietro Sollena, Luca Fania, Sofia Verkhovskaia, Pietro Quaglino, Clara De Simone, Giovanni Di Zenzo, Giuseppe Testa, Rosa Falcone
article en

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.

Acta Dermato VenereologicaVol. 106
Università Cattolica del Sacro Cuore (IT), Philipps University of Marburg (DE), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Ospedale Papa Giovanni XXIII (IT), Istituto Dermopatico dell'Immacolata (IT), Bambino Gesù Children's Hospital (IT), Department of Medical Sciences (BY), A. O. Ordine Mauriziano di Torino (IT), IRCCS Ospedale San Raffaele (IT), Ospedale Policlinico San Martino (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Usl Toscana Centro (IT), University of Florence (IT), University of Turin (IT), University of Genoa (IT)
Good health and well-being
Openalex Percentile: Top 7%
Autoimmune Bullous Skin Diseases
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