Introduction: Dermatitis herpetiformis (DH) is the cutaneous manifestation of gluten-related disorders and shares a common autoimmune pathogenesis with celiac disease. While TG3 antibodies are established markers, the diagnostic value of neo-epitope antibodies within a multiparametric serological approach remains incompletely defined.
Aim: To determine whether multiplex neo-epitope serology improves the diagnosis of DH compared with conventional single-marker testing and expands the clinical utility of routine gluten-related disorder serology.
Methods: Serum samples from 45 patients with DH and 27 disease controls (bullous pemphigoid or pemphigus vulgaris) were analyzed using the AESKUBLOTS® Gluten Related Disorders (GRD) IgA multiparametric immunoblot. The assay simultaneously quantified IgA antibodies against tTG, tTG-neo, TG3, mTG, mTG-neo, DGP, gliadin, Frazer's fraction, and total IgA. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis.
Results: TG3 (AUC 0.967), tTG-neo (AUC 0.960), and mTG-neo (AUC 0.957) demonstrated the highest diagnostic accuracy. Both tTG-neo and mTG-neo achieved 92.1% sensitivity with 100% specificity, while TG3 reached 89.5% sensitivity and 100% specificity. In contrast, conventional tTG IgA showed only 23.7% sensitivity despite maintaining 100% specificity. Simultaneous assessment of multiple disease-associated antibodies enabled comprehensive serological profiling within a single assay.
Discussion: Multiparametric assessment combining conventional and neo-epitope biomarkers substantially improves the serological characterization of DH. Inclusion of TG3 and neo-epitope antibodies within a routine gluten-related disorders panel may also facilitate recognition of patients with previously unrecognized DH undergoing serological evaluation for suspected celiac disease, whose cutaneous manifestations might otherwise remain overlooked.
Conclusion: Our findings support a shift from single-marker testing toward multiparametric serology in gluten-related disorders. Incorporating neo-epitope biomarkers markedly improves diagnostic sensitivity while maintaining excellent specificity. Beyond improving DH diagnosis, comprehensive antibody profiling has the potential to identify unsuspected DH during routine celiac disease work-up, thereby broadening the clinical value of multiplex serology.