Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies

Daniel Mimouni, Dagmar Foedinger, Dave J. Kouba, Seth J. Orlow, Klemens Rappersberger, James J. Sciubba, Olga V. Nikolskaia, Bernard A Cohen, Grant James Anhalt, Carlos H. Nousari

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)62-67
Number of pages6
JournalJournal of the American Academy of Dermatology
Volume51
Issue number1
DOIs
StatePublished - Jul 2004

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Desmoplakins
Pemphigus
Autoantibodies
Anti-Idiotypic Antibodies
Desmogleins
Indirect Fluorescent Antibody Technique
Immunoprecipitation
Antibodies
Plectin
Desmoglein 3
Antigens
Immunologic Tests
Immunoblotting
Epitopes

ASJC Scopus subject areas

  • Dermatology

Cite this

Mimouni, D., Foedinger, D., Kouba, D. J., Orlow, S. J., Rappersberger, K., Sciubba, J. J., ... Nousari, C. H. (2004). Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies. Journal of the American Academy of Dermatology, 51(1), 62-67. https://doi.org/10.1016/j.jaad.2003.11.051

Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies. / Mimouni, Daniel; Foedinger, Dagmar; Kouba, Dave J.; Orlow, Seth J.; Rappersberger, Klemens; Sciubba, James J.; Nikolskaia, Olga V.; Cohen, Bernard A; Anhalt, Grant James; Nousari, Carlos H.

In: Journal of the American Academy of Dermatology, Vol. 51, No. 1, 07.2004, p. 62-67.

Research output: Contribution to journalArticle

Mimouni, D, Foedinger, D, Kouba, DJ, Orlow, SJ, Rappersberger, K, Sciubba, JJ, Nikolskaia, OV, Cohen, BA, Anhalt, GJ & Nousari, CH 2004, 'Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies', Journal of the American Academy of Dermatology, vol. 51, no. 1, pp. 62-67. https://doi.org/10.1016/j.jaad.2003.11.051
Mimouni, Daniel ; Foedinger, Dagmar ; Kouba, Dave J. ; Orlow, Seth J. ; Rappersberger, Klemens ; Sciubba, James J. ; Nikolskaia, Olga V. ; Cohen, Bernard A ; Anhalt, Grant James ; Nousari, Carlos H. / Mucosal dominant pemphigus vulgaris with anti-desmoplakin autoantibodies. In: Journal of the American Academy of Dermatology. 2004 ; Vol. 51, No. 1. pp. 62-67.
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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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AU - Kouba, Dave J.

AU - Orlow, Seth J.

AU - Rappersberger, Klemens

AU - Sciubba, James J.

AU - Nikolskaia, Olga V.

AU - Cohen, Bernard A

AU - Anhalt, Grant James

AU - Nousari, Carlos H.

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N2 - 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.

AB - 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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