Abstract
Paraneoplastic pemphigus patients (PNP) develop a group of autoantibodies, among which those against envoplakin and periplakin are almost always found. Epitope mapping has indicated that the linker subdomains of the proteins harbor the major antigenic sites recognized by PNP sera. In order to detect specific autoantibodies for the diagnosis of PNP, we expressed recombinant proteins containing linker subdomains of human periplakin and envoplakin in a human kidney cell line, and used them as the antigens for ELISAs. We found that all of the sera from 16 PNP patients recognized these two recombinant proteins by ELISA, and sera from 20 pemphigus vulgaris (PV), 12 pemphigus foliaceus (PF), 20 bullous pemphigoid (BP), 2 Castleman’s tumor without PNP and 20 normal controls showed negative results. We also expressed the extracellular domain of desmoglein 3 (Dsg3) in the cell line, and used this recombinant Dsg3 as the ELISA antigen. Only 11 of our 16 PNP sera were positive, and most PV sera were positive. Our findings indicate that ELISAs using the recombinant proteins containing linker subdomains of envoplakin and periplakin expressed in a human cell line as the antigens are highly sensitive and specific for the diagnosis of PNP.
Similar content being viewed by others
References
Amagai M, Hashimoto T, Shimizu N et al (1994) Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus. J Clin Invest 94:59–67
Amagai M, Komai A, Hashimoto T et al (1999) Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus. Br J Dermatol 140:351–357
Amagai M, Nishikawa T, Nousari HC et al (1998) Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. J Clin Invest 102:775–782
Anhalt GJ (2004) Paraneoplastic pemphigus. J Investig Dermatol Symp Proc 9:29–33
Anhalt GJ, Kim SC, Stanley JR et al (1990) Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 323:1729–1735
Chen C, Okayama H (1987) High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7:2745–2752
Hashimoto T, Amagai M, Watanabe K et al (1995) Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. J Invest Dermatol 104:829–834
Helou J, Allbritton J, Anhalt GJ (1995) Accuracy of indirect immunofluorescence testing in the diagnosis of paraneoplastic pemphigus. J Am Acad Dermatol 32:441–447
Ishii K, Amagai M, Hall RP et al (1997) Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol 159:2010–2017
Mimouni D, Anhalt GJ, Lazarova Z et al (2002) Paraneoplastic pemphigus in children and adolescents. Br J Dermatol 147:725–732
Nousari HC, Deterding R, Wojtczack H et al (1999) The mechanism of respiratory failure in paraneoplastic pemphigus. N Engl J Med 340:1406–1410
Oursler JR, Labib RS, Ariss-Abdo L et al (1992) Human autoantibodies against desmoplakins in paraneoplastic pemphigus. J Clin Invest 89:1775–1782
Ruhrberg C, Hajibagheri MA, Parry DA et al (1997) Periplakin, a novel component of cornified envelopes and desmosomes that belongs to the plakin family and forms complexes with envoplakin. J Cell Biol 139:1835–1849
Wang J, Bu DF, Li T et al (2005) Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus. Br J Dermatol 153:558–564
Wang L, Bu D, Yang Y et al (2004) Castleman’s tumours and production of autoantibody in paraneoplastic pemphigus. Lancet 363:525–531
Zhang B, Zheng R, Wang J et al (2006) Epitopes in the linker subdomain region of envoplakin recognized by autoantibodies in paraneoplastic pemphigus patients. J Invest Dermatol 126:832–840
Zillikens D, Mascaro JM, Rose PA et al (1997) A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid. J Invest Dermatol 109:679–683
Acknowledgment
This work was sponsored by the National Natural Science Foundation of China (Grant number: 30671890).
Conflict of interest statement
The authors state no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, Y., Li, J. & Zhu, X. Detection of anti-envoplakin and anti-periplakin autoantibodies by ELISA in patients with paraneoplastic pemphigus. Arch Dermatol Res 301, 703–709 (2009). https://doi.org/10.1007/s00403-008-0901-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-008-0901-y