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

Background: Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. Data on clinical and immunological features of gliptin-associated bullous pemphigoid (GABP) are controversial. Objective: This study aims to clinically and immunologically characterize a large cohort of GABP patients to get insight into the pathophysiology of this emerging drug-induced variant of BP. Methods: Seventy-four GABP patients were prospectively enrolled and characterized from nine different Italian Dermatology Units between 2013 and 2020. Results: Our findings demonstrate that in GABP patients: i) the non-inflammatory phenotype which is characterized by low amounts of circulating and skin infiltrating eosinophils is frequently found; ii) IgG, IgE and IgA humoral response to BP180 and BP230 antigens is reduced in frequency and titers when compared with idiopathic BP; iii) IgG reactivity targets multiple BP180 epitopes other than NC16A. Limitations: A limitation of the study is the control group that did not comprise only type 2 diabetes mellitus BP patients. Conclusions: GABP patients show peculiar features of anti-BP180 and -BP230 humoral response laying the foundations for diagnostic improvements and to get novel insights into understanding the mechanism of BP onset.