Peptide Epitopes of NC16A BP180 in the Diagnostics of Bullous Pemphigoid

Bullous pemphigoid is a severe autoimmune blistering skin disorder causing significant morbidity and mortality among the elderly. Improved diagnostic strategies rely on the identification of autoantigen epitopes recognized by pathogenic autoantibodies. Continuous (linear) peptide epitopes, unlike conformational epitopes in recombinant proteins, offer advantages such as chemical stability, reproducibility, and lower production costs, making them attractive for diagnostic assay development. To identify relevant linear epitopes, a microarray of overlapping peptides spanning the NC16A domain of BP180 and the C-terminus of BP230 autoantigens was screened with sera of 13 patients with bullous pemphigoid and 2 control sera. A 25-mer peptide of NC16A, termed Pep7-NC16A, was evaluated by ELISA in 2 independent patient cohorts (n = 35 and 26 bullous pemphigoid cases, n = 48 and 53 controls). Pep7-NC16A ELISA showed sensitivity of 71% and 62% and specificity of 92% and 98%, with area under the curve values of 0.92 and 0.754 (P < .001). Reactivity strongly correlated with commercial BP180 NC16A ELISA (r = 0.72, P < .0001). In this study, we demonstrate the diagnostic potential of synthetic peptide in bullous pemphigoid. The identified epitope could also serve as a potential biomarker for BP180-associated conditions or future peptide-based immunotherapies.