Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies - 24/08/11

Doi : 10.1016/j.jaad.2003.11.051

Daniel Mimouni, MD ^a, Dagmar Foedinger, MD ^c, Dave J Kouba, MD, PhD ^a, Seth J Orlow, MD, PhD ^d, Klemens Rappersberger, MD ^c, James J Sciubba, DMD, PhD ^b, Olga V Nikolskaia, MD ^a, Bernard A Cohen, MD ^a, Grant J Anhalt, MD ^a, Carlos H Nousari, MD ^e,^⁎
From the Departments of Dermatology^a and Otolaryngology—Head and Neck Surgery^b of Johns Hopkins University; and the Departments of Dermatology at the University of Vienna^c; New York University^d; and the University of Pennsylvania^eUSA

Reprint requests: Carlos H. Nousari, MD. Division of Dermatopathology, Department of Dermatology, University of Pennsylvania, 3600 Spruce St, Maloney Building Second Floor, Philadelphia, PA 19104.

Baltimore, Maryland; New York, New York; Philadelphia, Pennsylvania; and Vienna, Austria

Abstract

Background

Anti-desmoplakin (DP) antibodies are present in paraneoplastic pemphigus (PNP) as a component of a complex humoral autoimmune reaction characterized by antibodies against proteins of the plakin family, desmogleins, and an unidentified 170 kd protein. Anti-DP antibodies have also been rarely identified in other blistering diseases. The significance of anti-DP antibodies in the pathogenesis of bullous diseases is unclear.

Observation

We studied 3 patients with severe and chronic mucosal dominant pemphigus vulgaris (PV). In addition to anti-desmoglein 3 antibodies, these patients had anti-DP autoantibodies, demonstrable by immunofluorescence (IF), immunoprecipitation (IP), and indirect immunoelectromicroscopy (IIEM). This finding suggested these patients may have had PNP and not PV. However, antibodies against periplakin, envoplakin, bullous pemphigoid antigen 1 (BPAG 1), plectin, and 170 kd PNP antigen could not be detected using IP and immunoblotting. Extensive and repeated investigations for an underlying neoplasm throughout the follow-up period were consistently negative for all patients.

Conclusion

This study demonstrates that anti-DP antibodies without the presence of any other anti-plakin antibodies are not specific for PNP, and are present in some cases of PV. Cellular disadhesion induced by anti-desmoglein antibodies can trigger an epitope-spreading phenomenon with a secondary formation of autoantibodies against desmoplakins, intracellular desmosomal antigens. The role of anti-DP antibodies in the pathogenesis of these PV patients is still unclear. The presence of anti-DP antibodies will produce a false positive serologic interpretation for the diagnosis of PNP especially if one uses only indirect IF on murine bladder, the most commonly employed screening test to identify PNP. More specific immunologic tests are required in this subset of patients with PV.

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