Comparison of C3d immunohistochemical staining to ELISA and immunofluorescence for diagnosis of bullous pemphigoid

Abstract Background Bullous pemphigoid (BP), the most common autoimmune blistering disease, may be diagnostically challenging. Direct immunofluorescence (DIF), indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and recently, C3d immunohistochemistry (IHC), are used as adjuncts to diagnosis. Objective To compare C3d IHC to DIF, IIF, and ELISA testing in BP diagnosis. Methods C3d IHC was performed on skin biopsies from a total of 51 patients (27 BP patients and 24 patients with other blistering diseases) and compared to DIF and IIF, using anti-BP180 or anti-BP230 ELISA results as the gold standard. Results We found C3d IHC, DIF and IIF had similar sensitivity (74.1%, 63.1%, 70.4%), specificity (95.8%, 100%, 100%), positive predictive value (95.2%, 100%, 100%), and negative predictive value (76.7%, 70.6%, 75%) for BP. Cases with positive C3d IHC, DIF and IIF had significantly higher anti-BP180 and anti-BP230 by ELISA than cases with negative testing (p Limitations This was a single-center, retrospective study. Conclusion Our study compared C3d IHC to DIF and IIF in BP diagnosis, demonstrating C3d IHC on fixed tissue provides similar diagnostic utility to immunofluorescence and ELISA.