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Comparison of C3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid - 19/06/20

Doi : 10.1016/j.jaad.2020.02.020 
Leo L. Wang, PhD, MS a, Ata S. Moshiri, MD, MPH e, Roberto Novoa, MD b, Cory L. Simpson, MD, PhD a, Junko Takeshita, MD, PhD, MSCE a, c, Aimee S. Payne, MD, PhD a, Emily Y. Chu, MD, PhD a, d,
a Department of Dermatology, the University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 
b Department of Pathology and Dermatology, Stanford University, Perelman School of Medicine, University of Pennsylvania, Stanford, California 
c Department of Biostatistics Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 
d Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 
e Division of Dermatology, University of Washington, Seattle, Washington 

Correspondence and reprint requests to: Emily Y. Chu, MD, PhD, Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, 2 Maloney Building, 3600 Spruce St, Philadelphia, PA 19104.Department of DermatologyPerelman School of Medicine at the University of Pennsylvania2 Maloney Building3600 Spruce StPhiladelphiaPA19104

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 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.

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Key words : bullous pemphigoid, C3d immunohistochemistry, diagnosis, direct immunofluorescence, ELISA, indirect immunofluorescence

Abbreviations used : BMZ, BP, CI, DIF, ELISA, IHC, IIF, ROC, TBS


Plan


 Funding sources: Dr Simpson is supported by a Dermatology Foundation Physician-Scientist Career Development Award. Dr Takeshita is supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-068433. This study was supported by a Dermatology Foundation Dermatopathology Career Development Award to Dr Chu.
 Conflicts of interest: Dr Novoa has served as consultant for Enspectra Health and received speaker's honoraria from Novartis Argentina and HealthCert for work unrelated to this manuscript. Dr Takeshita receives a research grant to the Trustees of the University of Pennsylvania from Pfizer Inc for work that is unrelated to this manuscript and received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly. Dr Payne has served as a consultant for SyntImmune Inc, holds equity in Cabaletta Bio, Inc, and has patents licensed by Novartis and Cabaletta Bio, Inc, focused on cellular therapies for autoimmune diseases. Drs Wang, Moshiri, Simpson, and Chu have no conflicts of interest to declare.
 IRB approval status: Use of human specimens in this study was provided through University of Pennsylvania Institutional Review Board-approved protocol #820338.


© 2020  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 83 - N° 1

P. 172-178 - juillet 2020 Retour au numéro
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