Desmoglein 3-ELISA: a pemphigus vulgaris-specific diagnostic tool.

BACKGROUND Pemphigus vulgaris (PV) is an autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies against desmoglein 3 (Dsg3), an epidermal desmosomal adhesion protein of the cadherin family. Cloning of the Dsg3 gene and expression of the protein in a native conformation enabled the recent development of a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for the detection of PV autoantibodies. OBJECTIVES To evaluate serum samples from patients with PV and other dermatologic diseases for anti-Dsg3 antibodies. To compare ELISA values with autoantibody titers obtained by classic indirect immunofluorescence (IIF). DESIGN Serum samples from patients with PV and various other bullous and nonbullous skin diseases were tested for anti-Dsg3 reactivity by ELISA. SETTING Ambulatory and hospitalized patients from a university hospital. PATIENTS Fifty-two serum samples from 11 patients with PV, and serum samples from 11 patients with bullous pemphigoid, 12 patients with other bullous diseases, 22 patients with various nonbullous skin disorders, and 10 healthy individuals were tested. RESULTS Forty-seven (98%) of 48 serum samples from patients with PV that were positive by IIF on monkey esophagus were also reactive by Dsg3-ELISA, whereas 4 of 4 IIF-negative PV serum samples showed no reactivity by ELISA. In addition, negative ELISA results were obtained from 11 of 11 serum samples from patients with bullous pemphigoid, 10 of 12 serum samples from patients with other bullous skin disorders, 7 of 9 serum samples from patients with autoimmune-connective tissue diseases, and 13 of 13 serum samples from patients with other nonbullous skin diseases. Interestingly, 1 patient with paraneoplastic pemphigus had positive ELISA results. There was a positive correlation (r = 0.654) between ELISA values and IIF titers within the whole population with PV. In addition, when multiple serum samples from 1 patient with PV sampled over a 2-year period were tested, ELISA reactivity paralleled both the IIF titers and the clinical course. CONCLUSION The Dsg3-ELISA is a sensitive, objective, and PV-specific test that should be considered as an adjunct test for the management of patients with PV.

[1]  C. Loomis,et al.  Architectural organization of filiform papillae in normal and black hairy tongue epithelium: dissection of differentiation pathways in a complex human epithelium according to their patterns of keratin expression. , 1999, Archives of dermatology.

[2]  T. Nishikawa,et al.  Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. , 1998, The Journal of clinical investigation.

[3]  M. Mahoney,et al.  Explanation for localization of blisters in pemphigus patients , 1998 .

[4]  Y. Kwon,et al.  cDNA cloning of the 210-kDa paraneoplastic pemphigus antigen reveals that envoplakin is a component of the antigen complex. , 1997, The Journal of investigative dermatology.

[5]  T. Nishikawa,et al.  Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. , 1997, Journal of immunology.

[6]  J. Bystryn,et al.  Sensitivity of indirect immunofluorescence, substrate specificity, and immunoblotting in the diagnosis of pemphigus. , 1997, Journal of the American Academy of Dermatology.

[7]  T. Nishikawa,et al.  Pemphigus vulgaris antigen (desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients. , 1996, The Journal of investigative dermatology.

[8]  T. Nishikawa,et al.  Conformational epitopes of pemphigus antigens (Dsg1 and Dsg3) are calcium dependent and glycosylation independent. , 1995, The Journal of investigative dermatology.

[9]  T. Nishikawa,et al.  Antigen-specific immunoadsorption of pathogenic autoantibodies in pemphigus foliaceus. , 1995, The Journal of investigative dermatology.

[10]  T. Nishikawa,et al.  A case of pemphigus vulgaris showing reactivity with pemphigus antigens (Dsg1 and Dsg3) and desmocollins. , 1995, The Journal of investigative dermatology.

[11]  M. Amagai,et al.  Characterization of paraneoplastic pemphigus autoantigens by immunoblot analysis. , 1994, The Journal of investigative dermatology.

[12]  T. Nishikawa,et al.  Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus. , 1994, The Journal of clinical investigation.

[13]  C. Lebbé,et al.  Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris. , 1994, The Journal of investigative dermatology.

[14]  M. Amagai,et al.  Extracellular domain of pemphigus vulgaris antigen (desmoglein 3) mediates weak homophilic adhesion. , 1994, The Journal of investigative dermatology.

[15]  K. V. Ratnam,et al.  Pemphigus in remission: value of negative direct immunofluorescence in management. , 1994, Journal of the American Academy of Dermatology.

[16]  M. Amagai,et al.  Autoantibodies against the amino-terminal cadherin-like binding domain of pemphigus vulgaris antigen are pathogenic. , 1992, The Journal of clinical investigation.

[17]  Masayuki Amagai,et al.  Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion , 1991, Cell.

[18]  S. Kim,et al.  Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia , 1991, The New England journal of medicine.

[19]  Xunzhang Wang,et al.  Baculovirus vectors for multiple gene expression and for occluded virus production. , 1991, Gene.

[20]  R. Phelps,et al.  Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin. , 1991, The Journal of investigative dermatology.

[21]  T. Nishikawa,et al.  Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. , 1990, The Journal of investigative dermatology.

[22]  M. S. Steinberg,et al.  A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus. , 1986, Journal of immunology.

[23]  L. Ivanyi,et al.  Relationship between the serum autoantibody titers and the clinical activity of pemphigus vulgaris. , 1985, Oral surgery, oral medicine, and oral pathology.

[24]  E. Beutner,et al.  Immunofluorescence Tests , 1985, International journal of dermatology.

[25]  M. Yaar,et al.  Pemphigus antibodies identify a cell surface glycoprotein synthesized by human and mouse keratinocytes. , 1982, The Journal of clinical investigation.

[26]  J. Voorhees,et al.  Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease. , 1982, The New England journal of medicine.

[27]  S. O'loughlin,et al.  Fate of pemphigus antibody following successful therapy. Preliminary evaluation of pemphigus antibody determinations to regulate therapy. , 1978, Archives of dermatology.

[28]  J. Schiltz,et al.  Production of epidermal acantholysis in normal human skin in vitro by the IgG fraction from pemphigus serum. , 1976, The Journal of investigative dermatology.

[29]  S. Katz,et al.  The Use of Human Skin for the Detection of Antiepithelial Autoantibodies , 1969 .

[30]  G. Giudice,et al.  Pemphigus Foliaceus and Pemphigus Vulgaris , 1998 .

[31]  A. Ahmed,et al.  Anti-intercellular substance antibodies. Presence in serum samples of 14 patients without pemphigus. , 1983, Archives of dermatology.

[32]  Ahmed Ar,et al.  Anti-Intercellular Substance Antibodies: Presence in Serum Samples of 14 Patients Without Pemphigus , 1983 .

[33]  T. Fitzpatrick.  Dermatology in general medicine : textbook and atlas , 1979 .

[34]  G. Lazarus,et al.  Anti-epidermal-cell-surface pemphigus antibody detaches viable epidermal cells from culture plates by activation of proteinase. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[35]  K. Wolff,et al.  Ultrastructural Localization of Pemphigus Autoantibodies within the Epidermis , 1971, Nature.

[36]  S. Katz,et al.  The use of human skin for the detection of anti-epithelial autoantibodies. A diagnostic and prognostic test. , 1969, The Journal of investigative dermatology.