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Study |

Detection of IgA Autoantibodies to Desmogleins by an Enzyme-Linked Immunosorbent Assay:  The Presence of New Minor Subtypes of IgA Pemphigus FREE

Takashi Hashimoto, MD; Ayako Komai, MD; Yuko Futei, MD; Takeji Nishikawa, MD; Masayuki Amagai, MD, PhD
[+] Author Affiliations

From the Departments of Dermatology, Kurume University School of Medicine, Fukuoka, Japan (Drs Hashimoto and Komai); and Keio University School of Medicine, Tokyo, Japan (Drs Futei, Nishikawa, and Amagai).


Arch Dermatol. 2001;137(6):735-738. doi:10-1001/pubs.Arch Dermatol.-ISSN-0003-987x-137-6-dst00067.
Text Size: A A A
Published online

Objective  To examine the frequency of antidesmoglein 1 (Dsg1) and antidesmoglein 3 (Dsg3) IgA autoantibodies in IgA pemphigus.

Design  We developed an enzyme-linked immunosorbent assay against recombinant Dsg1 and Dsg3 to detect IgA autoantibodies.

Patients  Twenty-two patients with IgA pemphigus were studied. Among them, 10 patients had subcorneal pustular dermatosis type, 9 patients had intraepidermal neutrophilic IgA dermatosis type, and 3 patients had pemphigus foliaceus–like clinical features.

Results  Of the 22 cases of IgA pemphigus, 3 cases were positive for anti-Dsg1 IgA antibodies and only 1 case was positive for anti-Dsg3 IgA antibodies. In those 4 cases, there were no IgA autoantibodies against other components of the keratinocyte cell surfaces because preincubation with the respective recombinant desmogleins removed the immunoreactivity on immunofluorescence. All 10 patients with subcorneal pustular dermatosis type IgA pemphigus were positive against desmocollin 1 expressed on COS-7 cells. No target antigen was detected in the other 8 cases.

Conclusions  Desmogleins were recognized by IgA antibodies of a few patients with IgA pemphigus. Considering that subcorneal pustular dermatosis type IgA pemphigus recognizes desmocollin 1, autoimmune targets of IgA pemphigus are more heterogeneous than previously considered.

Figures in this Article

DESMOSOMAL cadherins are of 2 types, desmoglein (Dsg) and desmocollin (Dsc), both of which occur as 3 isoforms, Dsg1, Dsg2, and Dsg3 and Dsc1, Dsc2, and Dsc3.1,2 Classic pemphigus showing IgG antikeratinocyte cell surface autoantibodies are divided into pemphigus foliaceus (PF) and pemphigus vulgaris, that react with Dsg1 and Dsg3.27 We have developed a novel enzyme-liked immunosorbent assay (ELISA) using recombinant proteins of Dsg1 and Dsg3 produced by baculovirus expression.810 This ELISA has been shown to be a highly sensitive and specific assay to detect autoantibodies in the serum samples of patients with PF and pemphigus vulgaris.

However, patients with vesiculopustular skin lesions that have anti–cell surface antibodies of the IgA class exclusively have been identified in patients and are commonly called "IgA pemphigus."11,12 IgA pemphigus is also divided into 2 major subtypes, the intraepidermal neutrophilic IgA dermatosis (IEN)13,14 and the subcorneal pustular dermatosis (SPD).15,16 The results of previous studies of the target antigens for IgA pemphigus were controversial.11,12 Standard immunoblotting showed no convincing reactivity with any known epidermal component proteins, probably because the epitopes for IgA pemphigus are conformation dependent and cannot be detected by immunoblotting. In addition, conventional immunoprecipitation cannot be used to detect antigens for IgA antibodies. Therefore, in a previous study,17 we developed a novel assay using complementary DNA transfection to COS-7 cells to identify conformation-dependent epitopes for IgA antibodies. Using the assay, we showed that the antigen for the SPD type IgA pemphigus is Dsc1,17 although the antigen for the IEN type IgA pemphigus was not identified.

Our aim in this study was to examine whether IgA antibodies in IgA pemphigus serum samples react with Dsg1 and Dsg3, ie, classic pemphigus antigens. To achieve this we modified the previously established ELISA of Dsg1 and Dsg3 baculoproteins to develop a new ELISA for detecting IgA antibodies to Dsg1 and Dsg3. Using this modified assay, we found that Dsg1 and Dsg3 were recognized by IgA antibodies of a few patients with IgA pemphigus.

PATIENTS

We collected serum samples from 22 patients with confirmed IgA pemphigus showing antikeratinocyte cell surface antibodies of the IgA class exclusively. Ten and 9 patients showed typical clinical and histopathologic features of the SPD type and the IEN type, respectively. Three patients had clinical and pathologic features resembling PF and were diagnosed as PF-like IgA pemphigus or IgA herpetiform pemphigus, although no IgG anti–cell surface antibodies were detected. Some of the cases tested in this study have been reported as a single case report.1316,1820 Serum samples obtained from 50 normal volunteers were used as controls. Immunofluorescence of normal human skin sections was performed using a standard method.21 Preparation of mammalian cell expression constructs of human Dsc1, 2, and 3, transfection into COS-7 cells, and the detection of IgA antibodies to desmocollins were described previously.17

METHODS
ELISA of Dsg1 and Dsg3 Baculoproteins for Detecting IgA Antibodies

Enzyme-linked immunosorbent assay to detect IgA antibodies against Dsg1 and Dsg3 was developed by modifying the established ELISA for IgG antibodies.8,9 Briefly, secreted forms of recombinant Dsg1 and Dsg3 were produced in High Five (Invitrogen, San Diego, Calif) cells by infecting recombinant baculoviruses, purified on TALON-affinity metal resin (CLONTECH Laboratories, Palo Alto, Calif), and 10 µg/mL of the recombinant protein was coated on 96-well microtiter plates, as described previously.9 All serum samples were diluted 200-fold and incubated for 1 hour at room temperature on the Dsg-coated plates. After washing 3 times with a phosphate-buffered saline solution with 0.13% polysorbate (Tween) 20, pH 7.3, the plates were then incubated with horseradish peroxidase–conjugated mouse monoclonal antihuman IgA antibody (Medical and Biological Laboratories, Nagoya, Japan) for 1 hour at room temperature. After color development, the absorbance was measured at 450 nm using a microtiter plate reader (Bio-Rad Laboratories, Hercules, Calif). To set a cutoff value for the ELISA, we calculated a mean (SD) using normal control serum samples. For the IgA ELISA, the mean (SD) of 50 normal serum samples was 0.027 (0.006). If we set a cutoff value at mean + 3 SDs, it would be 0.045. However, considering a definite positive reactivity, we set the cutoff value in this study at 0.15 for the ELISA for IgA antibodies.

The ELISA was performed in duplicate for all serum samples, which always produced similar results; the mean value of the 2 results was used in this study. In some patients with IgA pemphigus, the ELISA was performed twice on different days and produced almost the same results, confirming the specificity and reproducibility of this assay.

Immunoadsorption Assay

Immunoadsorption assay was performed using a previously described method22,23 with some modifications. Patients' serum samples were serially diluted at 1:10, 1:40, and 1:160 with insect cell culture supernatant containing recombinant Dsg1 or Dsg3. After incubation at 4°C overnight, the diluted serum samples were used for indirect immunofluorescence using normal human skin sections as a substrate. Those serum samples were also incubated with the same dilutions of uninfected cell supernatants as controls for positive immunofluorescence staining.

IMMUNOFLUORESCENCE AND COMPLEMENTARY DNA TRANSFECTION TESTS

Indirect immunofluorescence of normal human skin sections revealed IgA anti–cell surface antibodies at a titer of 10 to 320 in the serum samples of all patients with IgA pemphigus, except for 1 patient who had IEN type IgA pemphigus, which showed typical clinical and histopathologic features but no clear immunofluorescence staining (data not shown). No IgG anti–cell surface antibodies were detected in any serum samples. As we previously reported, all serum samples from the 10 patients with SPD IgA pemphigus reacted with the cell surface in the uppermost epidermis, while the serum samples from patients with other types of IgA pemphigus showed variable reactivity either with the entire epidermis or the lower epidermis.17

As previously reported,17 complementary DNA transfection assay for IgA antibodies with Dsc1, 2, and 3 showed that all of the serum samples from the 10 patients with SPD type IgA pemphigus reacted clearly with Dsc1-expressing COS-7 cells, while none of the serum samples from patients with other types of IgA pemphigus reacted with any of the 3 Dscs (data not shown).

ELISA OF RECOMBINANT Dsg1 AND Dsg3 FOR DETECTING IgA ANTIBODIES

Of 9 cases of IEN type IgA pemphigus, one case reacted with Dsg1 and another case reacted relatively weakly with Dsg3 (Figure 1). None of the serum samples from the 10 patients with SPD type IgA pemphigus reacted with either Dsg1 or Dsg3. Interestingly, 2 of the 3 cases diagnosed as PF-like IgA pemphigus showed IgA antibodies against Dsg1. None of the 22 IgA pemphigus serum samples showed IgG antibodies with either Dsg1 or Dsg3 using the established ELISA for IgG antibodies.

Place holder to copy figure label and caption
Figure 1.

The results of enzyme-linked immunosorbent assay for IgA and IgG autoantibodies against desmoglein 1 (A) and desmoglein 3 (B) in various types of IgA pemphigus, which were subdivided into intraepidermal neurotrophilic dermatosis IgA (IEN) type, subcorneal pustular dermatosis (SPD) type, pemphigus foliaeus–like (PF-like), and normal control subjects. The dashed line is the cutoff value (optical density 450 nm = 0.15).

Graphic Jump Location
IMMUNOADSORPTION ASSAY

We further performed the immunoadsorption assay with the 4 serum samples containing anti-Dsg1 or anti-Dsg3 IgA autoantibodies (Table 1 and Figure 2). The immunoreactivity against cell surfaces in all 3 cases with IgA antibodies to Dsg1 was removed by preincubation with recombinant Dsg1, but not with recombinant Dsg3. The reactivity in the case with anti-Dsg3 antibodies was absorbed with recombinant Dsg3, but not with Dsg1. These results indicate that these serum samples did not contain IgA autoantibodies against other components of keratinocyte cell membranes.

Table Graphic Jump LocationResults of Immunoadsorption Assay With Antidesmoglein IgA Antibody–Positive Serum Samples*
Place holder to copy figure label and caption
Figure 2.

Immunoadsorption assay revealed that IgA immunoreactivity against keratinocyte cell surfaces in an IgA pemphigus serum sample (1:40 dilution) was removed by preincubation with culture supernatant containing recombinant desmoglein 1 (B), while it was not removed by preincubation with uninfected culture supernatant (A).

Graphic Jump Location

Although there are a few single case reports of IEN type IgA pemphigus reactive with either Dsg3 or Dsg1,20,24,25 findings from our previous immunoblotting studies for a series of IgA pemphigus serum samples did not show any reactivity with either Dsg. Our previous study using a complementary DNA transfection assay indicated that IgA antibodies in the serum samples of SPD type IgA pemphigus react exclusively with conformation-dependent epitopes on human Dsc1. Therefore, it is conceivable that IgA pemphigus may contain IgA antibodies reactive with such conformation-dependent epitopes on Dsg1 and Dsg3, the autoantigens for classic IgG type pemphigus. In this study, to detect antigens for IgA antibodies, we modified the ELISA of Dsg1 and Dsg3 baculoproteins, which is a highly sensitive and specific assay for IgG autoantibodies.8,9

Using this new ELISA for IgA antibodies, we found that 4 serum samples from 22 patients with IgA pemphigus reacted with either Dsg1 or Dsg3. Interestingly, 2 of 3 patients who were diagnosed as having PF-like IgA pemphigus had IgA antibodies to Dsg1. One of the 2 Dsg1-positive cases of PF-like IgA pemphigus has previously been reported as IgA pemphigus foliaceus.18 This may indicate that this group is a distinct subtype of IgA pemphigus, although it is necessary to define the cases of PF-like IgA pemphigus (or IgA PF) by accumulating more cases.

Furthermore, one serum sample from each of the 9 patients with IEN type IgA pemphigus reacted with Dsg1 and Dsg3, respectively. This may support the results of scattered case reports describing the presence of IgA antibodies to Dsg1 or Dsg3 in IgA pemphigus.24,25 These results also suggest that IEN type IgA pemphigus is heterogeneous in terms of its antigen molecules. As suggested previously by ultrastructural localization,26 the antigen reacted by IEN type IgA pemphigus seems to be different from desmosomal proteins. Further studies should reveal this autoantigen.

In contrast, none of the serum samples from the 10 patients with SPD type IgA pemphigus had IgA antibodies to either Dsg1 or Dsg3. This is consistent with the results that, in indirect immunofluorescence, IgA antibodies in SPD type IgA pemphigus react exclusively with the cell surface in the uppermost epidermis, which is different from the distribution of either Dsg1 (the whole epidermis, being stronger in the upper epidermis) or Dsg3 (the lower epidermis).11,17

Although found in very few cases, the presence of IgA antibodies against Dsg1 and Dsg3 indicated in this study made the understanding of commonly called IgA pemphigus more complicated. Future studies of more cases should clarify the clinical and immunopathologic characteristics of this interesting condition.

Accepted for publication January 16, 2001.

This study was supported in part by Grant-in-Aid for Scientific Research grants 09557065 (Dr Hashimoto) and 11470186 (Dr Hashimoto) from the Ministry of Education, Science, and Culture of Japan, Tokyo, and a grant from the Ministry of Health and Welfare of Japan, Tokyo.

We are grateful to all of the dermatologists who generously sent us the serum samples of IgA pemphigus.

Corresponding author: Takashi Hashimoto, MD, Department of Dermatology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan (e-mail: hashimot@med.kurume-u.ac.jp).

Buxton  RSCowin  PFranke  WW  et al.  Nomenclature of the desmosomal cadherins. J Cell Biol. 1993;121481- 483
Amagai  M Adhesion molecules, I: keratinocyte-keratinocyte interaction; cadherins and pemphigus. J Invest Dermatol. 1995;104146- 152
Stanley  JRYaar  MHawley-Nelson  PKatz  SI Pemphigus antibodies identify a cell surface glycoprotein synthesized by human and mouse keratinocytes. J Clin Invest. 1982;70281- 288
Stanley  JRKoulu  LKlaus-Kovtun  VSteinberg  MS A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus. J Immunol. 1986;1361227- 1230
Hashimoto  T Skin diseases related to abnormality in desmosomes and hemidesmosomes. J Dermatol Sci. 1999;2081- 84
Hashimoto  TOgawa  MMKonohana  ANishikawa  T Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. J Invest Dermatol. 1990;94327- 331
Amagai  MKlaus-Kovtun  VStanley  JR Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991;67869- 877
Ishii  KAmagai  MHall  RP  et al.  Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol. 1997;1592010- 2017
Amagai  MHashimoto  TKomai  A  et al.  Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus. Br J Dermatol. 1999;140351- 357
Ishii  KAmagai  MKomai  A  et al.  Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus. Arch Dermatol. 1999;135943- 947
Ebihara  THashimoto  TIwatsuki  K  et al.  Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis. J Invest Dermatol. 1991;97742- 745
Iwatsuki  KHashimoto  TEbihara  TTeraki  YNishikawa  TKaneko  F Intercellular IgA vesiculo-pustular dermatosis and related disorders: diversity of IgA anti-intercellular autoantibodies. Eur J Dermatol. 1991;37- 11
Huff  JCGolitz  LEKunke  KS Intraepidermal neutrophilic IgA dermatosis. N Engl J Med. 1985;3131643
Teraki  YAmagai  MHashimoto  TKusunoki  TNishikawa  T Intercellular IgA dermatosis of childhood: selective deposition of monomer IgA1 in the intercellular space of the epidermis. Arch Dermatol. 1991;127221- 224
Tagami  HIwatsuki  KIwase  YYamada  M Subcorneal pustular dermatosis with vesiculo-bullous eruption: demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J Dermatol. 1983;109581- 587
Hashimoto  TInamoto  NNakamura  KNishikawa  T Intercellular IgA dermatosis with clinical features of subcorneal pustular dermatosis. Arch Dermatol. 1987;1231062- 1065
Hashimoto  TKiyokawa  CMori  O  et al.  Human desmocollin 1 (Dsc1) is an autoantigen for subcorneal pustular dermatosis type of IgA pemphigus. J Invest Dermatol. 1997;109127- 131
Beutner  EHChorzelski  TPWilson  RM  et al.  IgA pemphigus foliaceus: report of two cases amd a review of the literature. J Am Acad Dermatol. 1989;2089- 97
Inazumi  TKikuchi  AHan-Yaku  HHashimoto  TNishikawa  T Intercellular IgA vesiculopustular dermatosis: an additional case and a review of the literature. Eur J Dermatol. 1997;7503- 507
Karpati  SAmagai  MLi  LWDmochowski  MHashimoto  THorvath  A Identification of desmoglein 1 as an autoantigen in a patient with intraepidermal neutrophilic IgA dermatosis type of IgA pemphigus. Exp Dermatol. 2000;9224- 228
Beutner  EHJordon  REChorzelski  TP The immunopathology of pemphigus and bullous pemphigoid. J Invest Dermatol. 1968;5163- 80
Amagai  MHashimoto  TShimizu  TNishikawa  T Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus. J Clin Invest. 1994;9459- 67
Amagai  MHashimoto  TGreen  KShimizu  NNishikawa  T Antigen-specific immunoadsorption of pathogenic autoantibodies in pemphigus foliaceus. J Invest Dermatol. 1995;104895- 901
Prost  CIntrator  LWechsler  J IgA autoantibodies bind to pemphigus vulgaris antigen in a case of intraepidermal neutrophilic IgA dermatosis. J Am Acad Dermatol. 1991;25846- 848
Wang  JKwon  JDing  XFairley  JAWoodley  DTChan  LS Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in intraepidermal neutrophilic IgA dermatosis. Am J Pathol. 1997;1501901- 1907
Akiyama  MHashimoto  TSugiura  MNishikawa  T Ultrastructural localization of autoantigens of intercellular IgA vesiculopustular dermatosis in cultured human squamous cell carcinoma cells. Arch Dermatol Res. 1992;284371- 373

Figures

Place holder to copy figure label and caption
Figure 1.

The results of enzyme-linked immunosorbent assay for IgA and IgG autoantibodies against desmoglein 1 (A) and desmoglein 3 (B) in various types of IgA pemphigus, which were subdivided into intraepidermal neurotrophilic dermatosis IgA (IEN) type, subcorneal pustular dermatosis (SPD) type, pemphigus foliaeus–like (PF-like), and normal control subjects. The dashed line is the cutoff value (optical density 450 nm = 0.15).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Immunoadsorption assay revealed that IgA immunoreactivity against keratinocyte cell surfaces in an IgA pemphigus serum sample (1:40 dilution) was removed by preincubation with culture supernatant containing recombinant desmoglein 1 (B), while it was not removed by preincubation with uninfected culture supernatant (A).

Graphic Jump Location

Tables

Table Graphic Jump LocationResults of Immunoadsorption Assay With Antidesmoglein IgA Antibody–Positive Serum Samples*

References

Buxton  RSCowin  PFranke  WW  et al.  Nomenclature of the desmosomal cadherins. J Cell Biol. 1993;121481- 483
Amagai  M Adhesion molecules, I: keratinocyte-keratinocyte interaction; cadherins and pemphigus. J Invest Dermatol. 1995;104146- 152
Stanley  JRYaar  MHawley-Nelson  PKatz  SI Pemphigus antibodies identify a cell surface glycoprotein synthesized by human and mouse keratinocytes. J Clin Invest. 1982;70281- 288
Stanley  JRKoulu  LKlaus-Kovtun  VSteinberg  MS A monoclonal antibody to the desmosomal glycoprotein desmoglein I binds the same polypeptide as human autoantibodies in pemphigus foliaceus. J Immunol. 1986;1361227- 1230
Hashimoto  T Skin diseases related to abnormality in desmosomes and hemidesmosomes. J Dermatol Sci. 1999;2081- 84
Hashimoto  TOgawa  MMKonohana  ANishikawa  T Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources. J Invest Dermatol. 1990;94327- 331
Amagai  MKlaus-Kovtun  VStanley  JR Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991;67869- 877
Ishii  KAmagai  MHall  RP  et al.  Characterization of autoantibodies in pemphigus using antigen-specific enzyme-linked immunosorbent assays with baculovirus-expressed recombinant desmogleins. J Immunol. 1997;1592010- 2017
Amagai  MHashimoto  TKomai  A  et al.  Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus. Br J Dermatol. 1999;140351- 357
Ishii  KAmagai  MKomai  A  et al.  Desmoglein 1 and desmoglein 3 are the target autoantigens in herpetiform pemphigus. Arch Dermatol. 1999;135943- 947
Ebihara  THashimoto  TIwatsuki  K  et al.  Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis. J Invest Dermatol. 1991;97742- 745
Iwatsuki  KHashimoto  TEbihara  TTeraki  YNishikawa  TKaneko  F Intercellular IgA vesiculo-pustular dermatosis and related disorders: diversity of IgA anti-intercellular autoantibodies. Eur J Dermatol. 1991;37- 11
Huff  JCGolitz  LEKunke  KS Intraepidermal neutrophilic IgA dermatosis. N Engl J Med. 1985;3131643
Teraki  YAmagai  MHashimoto  TKusunoki  TNishikawa  T Intercellular IgA dermatosis of childhood: selective deposition of monomer IgA1 in the intercellular space of the epidermis. Arch Dermatol. 1991;127221- 224
Tagami  HIwatsuki  KIwase  YYamada  M Subcorneal pustular dermatosis with vesiculo-bullous eruption: demonstration of subcorneal IgA deposits and a leukocyte chemotactic factor. Br J Dermatol. 1983;109581- 587
Hashimoto  TInamoto  NNakamura  KNishikawa  T Intercellular IgA dermatosis with clinical features of subcorneal pustular dermatosis. Arch Dermatol. 1987;1231062- 1065
Hashimoto  TKiyokawa  CMori  O  et al.  Human desmocollin 1 (Dsc1) is an autoantigen for subcorneal pustular dermatosis type of IgA pemphigus. J Invest Dermatol. 1997;109127- 131
Beutner  EHChorzelski  TPWilson  RM  et al.  IgA pemphigus foliaceus: report of two cases amd a review of the literature. J Am Acad Dermatol. 1989;2089- 97
Inazumi  TKikuchi  AHan-Yaku  HHashimoto  TNishikawa  T Intercellular IgA vesiculopustular dermatosis: an additional case and a review of the literature. Eur J Dermatol. 1997;7503- 507
Karpati  SAmagai  MLi  LWDmochowski  MHashimoto  THorvath  A Identification of desmoglein 1 as an autoantigen in a patient with intraepidermal neutrophilic IgA dermatosis type of IgA pemphigus. Exp Dermatol. 2000;9224- 228
Beutner  EHJordon  REChorzelski  TP The immunopathology of pemphigus and bullous pemphigoid. J Invest Dermatol. 1968;5163- 80
Amagai  MHashimoto  TShimizu  TNishikawa  T Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus. J Clin Invest. 1994;9459- 67
Amagai  MHashimoto  TGreen  KShimizu  NNishikawa  T Antigen-specific immunoadsorption of pathogenic autoantibodies in pemphigus foliaceus. J Invest Dermatol. 1995;104895- 901
Prost  CIntrator  LWechsler  J IgA autoantibodies bind to pemphigus vulgaris antigen in a case of intraepidermal neutrophilic IgA dermatosis. J Am Acad Dermatol. 1991;25846- 848
Wang  JKwon  JDing  XFairley  JAWoodley  DTChan  LS Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in intraepidermal neutrophilic IgA dermatosis. Am J Pathol. 1997;1501901- 1907
Akiyama  MHashimoto  TSugiura  MNishikawa  T Ultrastructural localization of autoantigens of intercellular IgA vesiculopustular dermatosis in cultured human squamous cell carcinoma cells. Arch Dermatol Res. 1992;284371- 373

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