More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase-4 Inhibitor (DPP4i)-Associated Bullous Pemphigoid: A Retrospective Cohort Study

Background!#!The clinical and immunological profile of patients with dipeptidyl peptidase-4 inhibitor (DPP4i)-associated bullous pemphigoid (BP) is inconsistent in the current literature.!##!Objectives!#!The aims were to investigate the clinical and immunological features of patients with DPP4i-associated BP and to examine whether there are intraclass differences between different DPP4i agents.!##!Methods!#!A retrospective cohort study was conducted, including all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral center.!##!Results!#!The study encompassed 273 patients with BP (mean age at diagnosis 79.1 ± 9.9 years), of whom 24 (8.8%) were associated with DPP4i. Sitagliptin was the prescribed agent for 17 patients (70.8%), and vildagliptin was prescribed in seven patients (29.2%). Relative to other patients with BP, patients with DPP4i-associated BP had more prominent truncal involvement (95.8% vs. 73.9%; P = 0.017), greater erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) subscore (29.8 ± 17.4 vs. 20.6 ± 14.4; P = 0.018), and lower levels of anti-BP180 NC16A (279.2 ± 346.1 vs. 572.2 ± 1352.0 U/ml; P = 0.009) and anti-BP230 (25.5 ± 47.8 vs. 128.6 ± 302.9 U/ml; P = 0.009) antibodies. Relative to patients with sitagliptin-associated BP, those with vildagliptin-associated BP had a lower seropositivity rate (57.1% vs. 94.1%, P = 0.031) and lower levels (96.7 ± 139.0 vs. 354.5 ± 376.5; P = 0.023) of anti-BP180 NC16A antibodies, and tended to present with higher erosion/blister BPDAI subscore (36.3 ± 9.6 vs. 25.8 ± 19.7; P = 0.095).!##!Conclusions!#!DPP4i-associated BP is characterized by a more severe blistering and erosive presentation despite lower levels of typically pathogenic antibodies

Presence of Cutaneous Complement Deposition Distinguishes between Immunological and Histological Features of Bullous Pemphigoid—Insights from a Retrospective Cohort Study

The practical implications of complement deposition in direct immunofluorescence (DIF) microscopy and its influence on the disease phenotype are poorly understood. We aimed to investigate whether the presence of complement deposition in DIF microscopy gives rise to differences in the morphological, immunological, and histological characteristics of patients with BP (bullous pemphigoid). We performed a retrospective study encompassing patients with BP in a specialized tertiary referral center. Logistic regression model was utilized to identify variables independently associated with complement deposition. The study included 233 patients with BP, of whom 196 (84.1%) demonstrated linear C3 deposition along the dermal-epidermal junction (DEJ) in DIF analysis. BP patients with C3 deposition had higher mean (SD) levels (645.2 (1418.5) vs. 172.5 (243.9) U/mL; p < 0.001) and seropositivity rate (86.3% vs.64.9%; p = 0.002) of anti-BP180 NC16A and less prevalent neutrophilic infiltrate in lesional skin specimens (29.8% vs. 52.4%; p = 0.041). C3 deposition was found positively associated with the detection of anti-BP180 NC16A autoantibodies (OR, 4.25; 95% CI, 1.38–13.05) and inversely associated with the presence of neutrophils in lesional skin (OR, 3.03; 95% CI, 1.09–8.33). To conclude, complement deposition influences the immunological and histological features of BP. These findings are in line with experimental data describing the pathogenic role of complement in BP