Evaluation of a Newly Available ELISA for Envoplakin Autoantibodies for the Diagnosis of Paraneoplastic Pemphigus

October 2015 | Volume 14 | Issue 10 | Original Article | 1103 | Copyright © October 2015

Jennifer Gall Powell MD,a,c Raminder K. Grover MD,a,b Richard W. Plunkett PhD,a,b
Kristina Seiffert-Sinha MD,a and Animesh A. Sinha MDa

aDepartments of Dermatology, School of Medicine and Biomedical Sciences, University of Buffalo Department of Dermatology, Buffalo, NY
bMicrobiology and Immunology, School of Medicine and Biomedical Sciences, University of Buffalo Department of Dermatology, Buffalo, NY
cBuffalo Veterans Affairs Medical Center, Buffalo, NY

IMPORTANCE: Paraneoplastic pemphigus (PNP) is routinely diagnosed by the presence of autoantibodies for desmoplakin by indirect immunofluorescence (IIF) on rat bladder epithelium (RBE). IIF on RBE has recently been found to be positive in select cases of other blistering disorders. A new ELISA that detects envoplakin autoantibodies has recently been developed for the diagnosis of PNP. In this study, we measure the specificity of IIF on RBE and compare it to the new ELISA.
OBSERVATIONS: We measured the specificity of IIF on RBE to be 86% which is on the lower end of the previously reported specificity of 83% to 98.9%. The ELISA for envoplakin autoantibodies has a technical sensitivity of 100%, diagnostic sensitivity of 83%, and specificity of 91%.
CONCLUSIONS AND RELEVANCE: This ELISA for envoplakin autoantibodies is now commercially available and technically easier to perform then the immunoblot. We recommend that this new ELISA serves as a confirmatory test in cases of a positive IIF on RBE given its higher specificity.

J Drugs Dermatol. 2015;14(10):1103-1106.


Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized clinically by painful erosive mucositis and a polymorphous skin eruption. The diagnosis of PNP is based on this distinctive clinical presentation as well as histologic findings, immunofluorescence, severe pulmonary involvement, presence of malignancy, which is most commonly lymphoproliferative, poor response to therapy, poor prognosis, and a distinct immunologic profile. The histologic findings characteristically include suprabasilar acantholysis, keratinocyte necrosis, and vacuolar interface dermatitis.
The distinct immunologic profile of PNP includes circulating antibodies to desmoplakin I and II, envoplakin, periplakin, desmoglein (Dsg) 1 and 3, and bullous pemphigoid major antigen.1 Autoantibodies for desmoplakin on indirect immunofluorescence (IIF) on rat bladder epithelium (RBE) and autoantibodies for envoplakin and periplakin on immunoblot are sensitive and specific for the diagnosis of PNP.2
Recent evidence suggests that desmoplakin autoantibodies can also be found in select cases of pemphigus vulgaris (PV), pemphigus foliaceous, bullous pemphigoid, and erythema multiforme major.3 The specificity of desmoplakin for PNP may be lower than previously thought. In the first part of this study, we measure the specificity of paraneoplastic specific desmoplakin antibodies detected by IIF on RBE for the diagnosis of PNP.
Based on the high sensitivity and specificity of immunoblotting for envoplakin and periplakin antibodies, an enzyme-linked immunosorbent assay (ELISA) for the detection of envoplakin (EUROIMMUN US, Morris Plains, New Jersey) has been developed.4 This ELISA has not been directly compared to the diagnostic gold standard for the diagnosis of PNP, IIF on RBE for paraneoplastic pemphigus antibodies, and immunoblot for envoplakin and periplakin antibodies. In the second part of this study, we compare these methodologies to determine the diagnostic usefulness of this ELISA.


Patient Population

Fourteen patients seen by the Department of Dermatology, University of Buffalo between 2010 and 2013 with the diagnosis of pemphigus vulgaris, active clinical disease, and available serum were retrospectively selected for the first phase of this study.
An independent set of 17 serum samples from patients with high clinical suspicion of PNP was retrospectively selected for the second phase of this study based on serum samples submitted to the Beutner Laboratories, Buffalo, NY, from 2012-2013.