Gliptin-associated bullous pemphigoid shows peculiar features of anti-BP180 and -BP230 humoral response: Results of a multicenter study

Adele Salemme; Luca Fania; Alessandra Scarabello; Marzia Caproni; Angelo Valerio Marzano; Emanuele Cozzani; Claudio Feliciani; Clara De Simone; Manuela Papini; Rosanna Rita Satta; Aurora Parodi; Feliciana Mariotti; Stefania Lechiancole; Giovanni Genovese; Francesca Passarelli; Francesca Festa; Barbara Bellei; Alessia Provini; Donatella Sordi; Sabatino Pallotta; Damiano Abeni; Cinzia Mazzanti; Biagio Didona; Giovanni Di Zenzo; Cutaneous Immunology Group of SIDeMaST

doi:10.1016/j.jaad.2022.02.036

Gliptin-associated bullous pemphigoid shows peculiar features of anti-BP180 and -BP230 humoral response: Results of a multicenter study

J Am Acad Dermatol. 2022 Jul;87(1):56-63. doi: 10.1016/j.jaad.2022.02.036. Epub 2022 Mar 1.

Authors

Adele Salemme¹, Luca Fania², Alessandra Scarabello³, Marzia Caproni⁴, Angelo Valerio Marzano⁵, Emanuele Cozzani⁶, Claudio Feliciani⁷, Clara De Simone⁸, Manuela Papini⁹, Rosanna Rita Satta¹⁰, Aurora Parodi⁶, Feliciana Mariotti¹, Stefania Lechiancole², Giovanni Genovese⁵, Francesca Passarelli¹¹, Francesca Festa², Barbara Bellei¹², Alessia Provini², Donatella Sordi², Sabatino Pallotta¹³, Damiano Abeni¹⁴, Cinzia Mazzanti², Biagio Didona¹⁵, Giovanni Di Zenzo¹⁶; Cutaneous Immunology Group of SIDeMaST

Affiliations

¹ Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy.
² First Dermatology Clinic, IDI-IRCCS, Rome, Italy.
³ Dermatology unit, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.
⁴ Rare Diseases Unit, Section of Dermatology, Department of Health Sciences, USL Toscana Centro, European Reference Network-Skin Member, University of Florence, Florence, Italy.
⁵ Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan, Italy.
⁶ DiSSal, Dermatology Clinic, San Martino Polyclinic Hospital-IRCCS, University of Genoa, Genoa, Italy.
⁷ Dermatology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
⁸ Institute of Dermatology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università del Sacro Cuore, Rome, Italy.
⁹ Dermatologic Clinic of Terni, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
¹⁰ Department of Medical, Surgical, and Experimental Sciences, University of Sassari, Sassari, Italy.
¹¹ Pathology Unit, IDI-IRCCS, Rome, Italy.
¹² Laboratory of Cutaneous Physiopathology and Integrated Center for Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, Rome, Italy.
¹³ Fifth Dermatology Clinic, IDI-IRCCS, Rome, Italy.
¹⁴ Clinical Epidemiology Unit, IDI-IRCCS, Rome, Italy.
¹⁵ Rare disease Unit, IDI-IRCCS, Rome, Italy.
¹⁶ Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy. Electronic address: [email protected].

PMID: 35240229
DOI: 10.1016/j.jaad.2022.02.036

Abstract

Background: Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. However, data on the clinical and immunologic features of gliptin-associated bullous pemphigoid (GABP) are controversial.

Objective: This study aimed to clinically and immunologically characterize a large cohort of GABP patients to get an insight into the pathophysiology of this emerging drug-induced variant of BP.

Methods: Seventy-four GABP patients were prospectively enrolled and characterized from 9 different Italian dermatology units between 2013 and 2020.

Results: Our findings demonstrated the following in the GABP patients: (1) a noninflammatory phenotype, which is characterized by low amounts of circulating and skin-infiltrating eosinophils, is frequently found; (2) immunoglobulin (Ig)G, IgE, and IgA humoral responses to BP180 and BP230 antigens are reduced in frequency and titers compared with those in patients with idiopathic BP; (3) IgG reactivity targets multiple BP180 epitopes other than noncollagenous region 16A.

Limitations: A limitation of the study is that the control group did not comprise only type 2 diabetes mellitus patients with BP.

Conclusion: GABP patients show peculiar features of anti-BP180 and -BP230 humoral responses, laying the foundation for diagnostic improvements and getting novel insights into understanding the mechanism of BP onset.

Keywords: BP180; autoantibody; bullous pemphigoid; epitope; gliptin; humoral response.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies
Autoantigens
Diabetes Mellitus, Type 2*
Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
Humans
Immunoglobulin G
Non-Fibrillar Collagens
Pemphigoid, Bullous*

Substances

Autoantibodies
Autoantigens
Dipeptidyl-Peptidase IV Inhibitors
Immunoglobulin G
Non-Fibrillar Collagens