Comparison of C3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid

Background: Bullous pemphigoid (BP), the most common autoimmune blistering disease, may be diagnostically challenging. Direct immunofluorescence (DIF), indirect immunofluorescence (IIF), enzymelinked 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 biopsy specimens from 51 patients (27 with BP and 24 with other blistering diseases) and compared to DIF and IIF, with anti-BP180 or anti-BP230 ELISA results used as the gold standard. Results: We found C3d IHC, DIF, and IIF had similar sensitivity (74.1%, 63.1%, and 70.4%), specificity (95.8%, 100%, and 100%), positive predictive value (95.2%, 100%, and 100%), and negative predictive value (76.7%, 70.6%, and 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<.0001). False-negative IIF results were associated with lower BP230 compared with true-positive results (P=.03). 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.