Dsg3 Enzyme-linked Immunosorbent Assay Research Articles

Evaluation of the Role of Oral Mucosal Direct Immunofluorescence and Salivary Desmoglein 1 and 3 Enzyme-Linked Immunosorbent Assay in Patients With Oral Mucosal Pemphigus.

Background:Pemphigus vulgaris (PV) is characterized by antibodies against desmosomal adhesion proteins desmoglein (Dsg) 1 and 3 which can be detected by direct immunofluorescence (DIF) or enzyme-linked immunosorbent assay (ELISA). Oral lesions usually precede cutaneous lesions and an early diagnosis can prevent mortality and morbidity. Dsg antibodies can be detected by ELISA in saliva of patients with oral mucosal pemphigus. This study compares oral mucosal DIF with the salivary Dsg1 and 3 ELISA.Materials and Methods:A total of 26 biopsy and/or DIF-proven PV patients with oral erosions without cutaneous lesions were included in the study. Biopsy of oral mucosa was taken for DIF by standard method. Saliva sample was obtained and processed for ELISA. The results were then compared.Results:Out of 26 patients, 22 (84.6%) had a positive oral mucosal DIF and four patients (15.4%) had negative DIF. Nine patients (34%) had positive salivary Dsg3 ELISA. Seven patients (27%) had positive salivary Dsg1 ELISA. Taking oral DIF as the gold standard, the sensitivity of salivary Dsg1 ELISA was 31.8% and of salivary Dsg3 ELISA was 40.9%.Conclusion:Although DIF is the gold standard for the diagnosis of PV, salivary Dsg1 and 3 ELISA can also be used in the diagnosis of oral pemphigus.

Serum and salivary IgG and IgA antibodies to desmoglein 3 in mucosal pemphigus vulgaris.

The use of saliva for the diagnosis of pemphigus vulgaris (PV) by enzyme-linked immunosorbent assay (ELISA) using desmoglein (Dsg)3 antigen has not been extensively documented, nor has the detection of serum IgA antibodies to Dsg3. (i) To establish whether whole saliva might provide a suitable alternative to serum for diagnosing and monitoring PV; (ii) to investigate whether anti-Dsg3 IgA antibodies can be detected in serum and saliva and (iii) to establish whether there is an association between serum or saliva anti-Dsg3 antibodies and disease severity. Precoated Dsg3 ELISA plates were used to test serum and/or saliva for IgG and IgA antibodies. Matched serum and whole saliva samples were collected from 23 patients with PV, 17 healthy subjects and 19 disease controls. All patients with PV, disease controls and six healthy controls provided matched parotid saliva. Whole saliva IgG antibodies to Dsg3 were detected in 14 of 23 patients (61%) and serum IgG antibodies were detected in 17 of 23 (74%) with a strong positive correlation. Serum IgA antibodies were detected in 14 of 23 patients with PV (61%) with a combined positivity (IgG and/or IgA antibodies to Dsg3) of 78% (18 of 23). We were unable to show IgA anti-Dsg3 antibodies in either whole or parotid saliva of patients with PV. Sequential samples showed that changes in IgG antibody titres in whole saliva were associated with a change in disease severity scores. Assay of salivary IgG antibodies to Dsg3 offers a diagnostic alternative to serum in the diagnosis and monitoring of PV. The role of anti-Dsg3 IgA antibodies requires further elucidation in the pathogenesis of PV.

Usefulness of enzyme-linked immunosorbent assay in the diagnosis of pemphigus and bullous pemphigoid in upper Egypt: correlation with intensity score

Background The availability of complementary DNA clones for pemphigus and pemphigoid antigens has led to the production of recombinant proteins representing epitopes of native antigens Dsg1, Dsg3, BP180 and BP230, and to the development of related enzyme-linked immunosorbent assay (ELISA) systems. Objective The aim of this study was to evaluate the diagnostic value of Dsg1, Dsg3, BP180 and BP230 ELISAs in upper Egypt patients, and to assess its correlation with the severity of diseases. Patients and methods Forty-six patients with pemphigus and bullous pemphigoid were enrolled. The diagnosis was confirmed by means of histopathology and direct immunofluorescence. Autoantibodies against Dsg1, Dsg3, BP180 and BP230 were assayed using ELISA in the serum of pemphigus and bullous pemphigoid patients. In pemphigus vulgaris, anti-Dsg1 and anti-Dsg3 antibody titre were raised above the cutoff value in 88.5 and 96.1% of patients, respectively. A strong positive correlation between the titre of anti-Dsg1 and Dsg3 and the total Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) in (mucocutaneous) pemphigus patients (P Conclusion ELISA can be considered an important step in the laboratory diagnosis of pemphigus and bullous pemphigoid, especially as it is a simple, noninvasive and fast manoeuvre. Anti-Dsg1 Ab and anti-Dsg3 Ab ELISA values are correlated with the disease activity of pemphigus. Anti-BP180 and anti-BP230 Ab ELISA values are correlated with the disease activity of bullous pemphigoid.

The Value of Anti-Desmoglein Enzyme-Linked Immunosorbent Assay in the Immunological Follow-Up of Pemphigus

Background: The value of anti-desmoglein 1 and 3 (Dsg1, Dsg3) enzyme-linked immunosorbent assay (ELISA) is controversial in the follow-up of pemphigus. Objective: To evaluate anti-desmoglein ELISA (Dsg ELISA) in the follow-up of pemphigus and compare ELISA with direct and indirect immunofluorescence in complete remission (CR). Methods: We performed a retrospective monocenter study of patients with pemphigus and consecutive sera samples collected at baseline (M0), 12 months (M12) and 24 or 36 months after M0 (M24/36). Tests were compared in CR and in active disease. Direct immunofluorescence and circulating autoantibodies were compared for patients with stable CR. Results: We included 36 patients. At M12, ELISA values did not differ between CR and active disease. At M24/36, Dsg3 but not Dsg1 ELISA values were lower in CR (p = 0.07). For 5/8 patients with stable CR, direct immunofluorescence and ELISA findings remained positive. Conclusion: In routine practice, Dsg ELISA seems to be of little interest for immunological follow-up of pemphigus.

A higher correlation of the antibody activities against the calcium-dependent epitopes of desmoglein 3 quantified by ethylenediaminetetraacetic acid-treated enzyme-linked immunosorbent assay with clinical disease activities of pemphigus vulgaris

BackgroundNonpathogenic anti-desmoglein (Dsg) 3 antibodies can be found in pemphigus vulgaris (PV) patients’ sera. Previously, ethylenediaminetetraacetic acid (EDTA)-treated enzyme-linked immunosorbent assay (ELISA) was found to detect only nonpathogenic anti-Dsg3 antibodies against the non-calcium (Ca2+)-dependent epitopes. ObjectiveWe examined whether the calculated anti-Dsg3 antibody titer for Ca2+-dependent epitopes, using the conventional and EDTA-treated ELISAs, correlated better with the disease activity of PV. MethodsWe analyzed 123 serum samples from 19 PV patients. Of these samples, there were 52 samples from 15 PV patients obtained in asymptomatic phases. The difference between conventional Dsg3 ELISA index and EDTA-treated Dsg3 ELISA index was calculated as the anti-Dsg3 antibody activity for Ca2+-dependent conformational epitopes (conformational Dsg3 ELISA index). We analyzed the correlation between Dsg3 ELISA index values and the pemphigus disease area index (PDAI). Moreover, we examined whether the conformational Dsg3 ELISA index fluctuated in parallel with the disease activity during clinical courses of 6 PV patients. We evaluated the pathogenicity of anti-Dsg3 antibodies detected in remission phases using a dissociation assay. ResultsThe conventional Dsg3 ELISA index showed a high positive rate in the asymptomatic phase of PV. By contrast, the conformational Dsg3 ELISA index showed a much closer correlation to the disease activity when monitored in individual cases. Nonpathogenic anti-Dsg3 antibodies were detected in these cases. ConclusionThe conformational Dsg3 ELISA index reflected the pathogenicity of anti-Dsg3 antibodies more accurately than the conventional Dsg3 ELISA index. Using both conventional and EDTA-treated ELISAs would be useful in monitoring the disease activity of PV.

Evaluation of commercially available ELISA assays as a tool for monitoring and managing pemphigus patients: a prospective study

Pemphigus is a potentially life-threatening auto-immune blistering disease and consequently it is important to monitor disease activity. To assess the usefulness of serial antibody titers in the management of pemphigus and to predict disease activity in the clinical follow-up of pemphigus patients. In this prospective observational study, seven patients with pemphigus vulgaris and three patients with pemphigus foliaceus were examined on a monthly basis for 24 months, or two-weekly during active disease. Disease activity was registered according to a new score system. A total of 158 samples were tested using commercial desmoglein (Dsg) 1 and Dsg3 enzyme-linked immunosorbent assay (ELISA) kits. The 20 U/mL cut-off for the anti-Dsg1 ELISA value was associated with a significantly higher risk of a skin activity score>0 (OR=7.91, 95% CI=1.71;36.65, p=0.01). A cut-off for disease activity at 5 gave an OR of 11.40 (95% CI=2.64;49.09, p=0.003). Dsg1 values of >15 had a sensitivity of 79.41% and specificity of 87.80% for predicting a relapse of skin disease in pemphigus patients. For Dsg3, no odds could be calculated for mucosal involvement, nor a predicting value for mucosal relapse. We conclude that only Anti-Dsg1 antibody ELISA values seem valuable in the follow-up of pemphigus patients and carry a predictive value. However, serial antibody titers cannot be seen as absolute indicators of disease activity and we believe that both Dsg1 and Dsg3 ELISA tests should be used with caution to monitor disease activity.

Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance

Antidesmoglein (anti-Dsg) 3 serum antibody titres are usually correlated with the disease activity of pemphigus vulgaris (PV), but some patients retain high titres even in remission. The aim of our study was to determine whether anti-Dsg3 antibodies in PV sera recognized calcium (Ca(2+) )-dependent or non-Ca(2+) -dependent epitopes, and to evaluate their pathogenicity. Dsg3 baculoprotein-coated enzyme-linked immunosorbent assay (ELISA) plates were treated with 0.5 mmol L(-1) ethylenediaminetetraacetic acid (EDTA). The binding ability of anti-Dsg3 monoclonal antibodies (mAbs) was analysed. Eight of the 83 patients with PV who were screened had elevated Dsg3 ELISA index values > 00 in remission. The binding ability of these PV sera was analysed. We evaluated the pathogenicity of anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes using a dissociation assay. The reactivity of pathogenic anti-Dsg3 mAbs against the Ca(2+) -dependent epitopes diminished markedly in the EDTA-treated ELISA, whereas no such reduction was observed in mAbs against the non-Ca(2+) -dependent epitopes. The sera of all the patients contained antibodies against both Ca(2+) -dependent and non-Ca(2+) -dependent epitopes. In six out of the eight patients, the ratio of antibodies against Ca(2+) -dependent to non-Ca(2+) -dependent epitopes decreased in remission. EDTA-treated Dsg3 baculoproteins adsorbed anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes, but the remnant PV antibodies retained the ability to induce acantholysis in the dissociation assay. We have established an assay to measure indirectly the titres of anti-Dsg3 serum antibodies against the Ca(2+) -dependent epitopes, based on the differences between EDTA-untreated and EDTA-treated ELISA index values, as a routine laboratory test to reflect the pathogenic anti-Dsg3 serum antibody titres more accurately.

Evaluation of desmoglein 1 enzyme-linked immunosorbent assay in the detection of serum antibodies in patients with pemphigus foliaceus.

Objective To evaluate the performance of desmoglein (Dsg)1 enzyme-linked immunosorbent assay (ELISA) in the detection of serum antibodies in patients with pemphigus foliaceus (PF). Methods Sera were obtained from 80 patients with PF and 132 human controls including 33 patients with bullous pemphigoid, 3 patients with linear IgA bullous dermatosis, 2 patients with acquired bullous epidermolysis, 20 patients with systemic lupus erythematosus (SLE), etc, and subjected to a random and blind test by Dsg1 ELISA and indirect immunofluorescence (IIF) on monkey oesophagus. Results The Dsg1 ELISA was positive in 75 (93.8%) patients with PF and 5 (3.8%) human controls (including 1 case of bullous pemphigoid, 1 case of SLE, 1 case of dermatomyositis, 1 case of eczema and 1 normal human control with indeterminate value), and IIF was positive in 71 (88.8%) patients with PF, but in none of the controls. The sensitivity and specificity was 93.8% (95% CI: 0.85 - 0.98) and 96.2% (95% CI: 0.91 - 0.99) respectively for Dsg1 ELISA in the serodiagnosis of PF, 88.8% (95% CI: 0.82 - 0.96) and 100% (95% CI: 0.96 - 1.00) respectively for IIF. There was no statistical difference in the sensitivities (P= 0.289) or specificities (P= 1.000) between the two test methods.Conclusions Dsg1 ELISA is a simple, sensitive and specific serological detection method, and can serve as an adjunct in the diagnosis of PF. Key words: Pemphigus; Desmoglein 1; Enzyme-linked immunosorbent assay; Fluorescent antibody technique,indirect

Serum and salivary desmoglein 1 and 3 enzyme‐linked immunosorbent assay in pemphigus vulgaris: correlation with phenotype and severity

To the best of our knowledge there is only one report about salivary desmoglein (Dsg) 1 and 3 enzyme-linked immunosorbent assay (ELISA) in pemphigus vulgaris (PV), whereas several studies have been performed on serum. To find the sensitivity of serum and salivary anti-Dsg1 and 3 antibodies in the diagnosis of PV, and to determine the relationship between disease severity and phenotype with antibody levels. Fifty new patients with PV were included in this study. The diagnosis of PV was confirmed by histopathology and direct immunofluorescence. Demographical data, disease severity and phenotypes were recorded on questionnaire sheets. Dsg1 and Dsg3 ELISA were performed on serum and salivary samples of patients and controls. Thirty-seven patients had mucocutaneous phenotype; whereas mucosal dominant and cutaneous dominant phenotypes were seen in 11 and 2 patients respectively. The sensitivities of serum anti-Dsg3 and anti-Dsg1 were 94% and 72% respectively. The sensitivities of salivary anti-Dsg3 and anti-Dsg1 antibodies were accordingly 94% and 70%. Compared with mucosal phenotype, serum and salivary anti-Dsg1 antibodies were significantly higher in the patients with mucocutaneous phenotype. Serum Dsg1 antibodies were related with cutaneous and serum Dsg3 antibodies with mucosal severity scores. Salivary Dsg1 antibodies were significantly correlated with mucosal severity (P=0.00); however there was no correlation between this antibody and cutaneous severity (P=0.07). Salivary Dsg3 antibodies were not correlated with mucosal severity (P=0.16). Saliva Dsg ELISA could be used for diagnosis of PV. Salivary Dsg1 antibodies had a significant correlation with mucosal severity.

Who Will Develop Pemphigus Foliaceus?

Pemphigus foliaceus (PF), an autoimmune blistering disorder, is characterized by the development of superficial cutaneous blisters in a seborrheic distribution, without mucosal involvement. Autoantibodies target the desmoglein 1 (Dsg1) antigen expressed on the surface of keratinocytes located in the superficial levels of the epidermis (Mahoney et al., 1999), and both sporadic PF and endemic PF can occur. Endemic PF, referred to as fogo selvagem (FS), is endemic to specific areas of the world, most notably Brazil, although it has also been described in Tunisia and Colombia (Abreu-Velez et al., 2003). Both genetic and environmental factors appear to play a role in the development of FS. Certain human leukocyte antigen (HLA) types appear to be at greatest risk: the HLA-DRB1*0102, HLA-DRB1*0404, and HLA-DRB1*1402 alleles (P < 0.005, relative risk, 14; Moraes et al., 1997). It has been hypothesized that the disease may be triggered by a local environmental agent(s) such as Simulium (a hematophagous insect), causing a cross-reactive anti-Dsg1 antibody response that leads to FS (Diaz et al., 2004). Endemic PF is of special interest, beyond its clinical impact on those affected, because it can serve as a model for organ-specific immune disease with both genetic and environmental components. FS appears to be caused by isotyperestricted, pathogenic anti-Dsg1 autoantibodies that are predominantly IgG4 (Warren et al., 2003) and that increase in concentration in serum upon progression from preclinical to clinical disease. Development of a predictive test for PF would benefit those at high risk, and it could also serve as an investigative tool. In an effort to develop such a test, Qaqish et al. (2009, this issue) used Dsg1 enzyme-linked immunosorbent assay in a study of 214 patients with FS and 261 healthy controls, randomly divided into training (50%), validation (25%), and test (25%) sets. IgG4 was found to be the best predictor of FS, with a sensitivity of 92% and specificity of 97%. The positive predictive value of this test in the endemic region of Brazil (which has an FS prevalence of 3%) was 49%. This was then validated by testing 11 patients with FS before and after clinical disease onset, as well as 60 Japanese patients with PF. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to http://

Diagnostic value of Dsg1 ELISA for pemphigus foliaceus: an appraisal

Pemphigus foliaceus, a dermatological immune disorder, usually presents with cutaneous blistering. Of the several diagnostic tools, enzyme-linked immunosorbent assay (ELISA) against desmoglein (Dsg) 1 is widely used. The diagnostic value of Dsg1 ELISA test was previously studied by others and gave differences in diagnostic power. In addition, most reports focused on small sample sizes. Therefore, a systematic meta-analysis was conducted to assess the diagnostic property of this test. In this paper, the author summarized the diagnostic value of Dsg1 ELISA for pemphigus foliaceus. In the literature, there are 4 published papers [1 – 4] on 232 cases and 446 controls (Table 1). The overall sensitivity and specificity are equal to 95.3 and 96.4 respectively. This supports the diagnostic usefulness of Dsg1 ELISA for diagnosing pemphigus foliaceus. Figure 1 Table 1. Reports on diagnostic value of Dsg1 ELISA for pemphigus folliculus

Autoantibodies in the Autoimmune Disease Pemphigus Foliaceus Induce Blistering via p38 Mitogen-Activated Protein Kinase-Dependent Signaling in the Skin

Pemphigus foliaceus (PF) is a human autoimmune blistering disease in which a humoral immune response targeting the skin results in a loss of keratinocyte cell-cell adhesion in the superficial layers of the epidermal epithelium. In PF, desmoglein-1-specific autoantibodies induce blistering. Evidence is beginning to accumulate that activation of signaling may have an important role in the ability of pathogenic pemphigus IgGs to induce blistering and that both p38 mitogen-activated protein kinase (MAPK) and heat shock protein (HSP) 27 are part of this signaling pathway. This study was undertaken to investigate the ability of PF IgGs to activate signaling as well as the contribution of this signaling pathway to blister induction in an in vivo model of PF. Phosphorylation of both p38 MAPK and HSP25, the murine HSP27 homolog, was observed in the skin of PF IgG-treated mice. Furthermore, inhibition of p38 MAPK blocked the ability of PF IgGs to induce blistering in vivo. These results indicate that PF IgG-induced blistering is dependent on activation of p38 MAPK in the target keratinocyte. Rather than influencing the immune system, limiting the autoantibody-induced intracellular signaling response that leads to target end-organ damage may be a more viable therapeutic strategy for the treatment of autoimmune diseases. Inhibition of p38 MAPK may be an effective strategy for the treatment of PF.

Anti‐desmoglein IgG autoantibodies in patients with pemphigus in remission

Desmoglein (Dsg) enzyme-linked immunosorbent assay (ELISA) is a highly sensitive and specific method to detect anti-Dsg3 and anti-Dsg1 IgG autoantibodies in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. Whereas ELISA index values fluctuate in parallel with disease activity, ELISA positivity during clinical remission has been observed. To determine the prevalence of positive Dsg ELISA index values during clinical remission. To ascertain how positive Dsg ELISA scores during remission compare with those during active disease. Dsg ELISA was performed on serum samples of PV and PF patients taken during remission (lesion-free >or= 3 months on <or= 15 mg or <or= 5 mg/day prednisolone) and active disease. We used a modified ELISA protocol with optimal serum dilutions in sera with very high initial index values, as we previously described. When remission was defined as no eruption >or= 3 months with <or= 15 mg/day prednisolone, 20 of 43 PV patients (46.5%) and 4 of 12 PF patients (33.3%) showed Dsg3 and Dsg1 ELISA positivity, respectively. With <or= 5 mg/day, 6 of 17 PV (35.3%) and 1 of 6 PF patients (16.7%) showed Dsg3 and Dsg1 ELISA positivity, respectively. The index value of each ELISA-positive remission serum was consistently lower than that of its corresponding active disease serum. We observed consistent correlation between ELISA index values and indirect immunofluorescence titres. Circulating anti-Dsg IgG autoantibodies are found in a considerable percentage of pemphigus patients in remission, who have high levels of antibody production during active stages.

Disease Progression From Mucosal to Mucocutaneous Involvement in a Patient With Desquamative Gingivitis Associated With Pemphigus Vulgaris

Pemphigus vulgaris (PV) frequently begins with oral lesions and progresses to skin lesions. A patient is described who developed skin lesions during follow-up and whose only initial symptom was desquamative gingivitis (DG). A 31-year-old woman presented with a 2-month history of painful gingiva. The diagnosis of PV was made according to clinical, histopathological, and immunofluorescent criteria. Topical corticosteroid (0.1% triamcinolone acetonide) was provided for the treatment of DG. Evaluation of the circulating autoantibody titers to desmoglein (Dsg)1 and Dsg3 was conducted by enzyme-linked immunosorbent assay (ELISA). The gingival PV lesions went into remission with the use of topical corticosteroid, although the patient experienced occasional recurrent oral lesions that required retreatment. She had regular follow-ups and remained relatively stable for several months. However, relapse and worsening of the oral lesions and the onset of skin lesions occurred after 26 months. Using ELISA, a change in the autoantibody profile corresponding to the transition from mucosal PV to mucocutaneous PV was confirmed. In all ELISA studies conducted throughout the course of the patient's disease, the Dsg3 ELISA was consistently high ranging from 150 to 200. However, the Dsg1 ELISA remained low, ranging from 10 to 30. After 26 months, Dsg3 (index value of 150) and Dsg1 (index value of 114) ELISA levels were elevated, consistent with the transition to mucocutaneous PV. In cases in which the lesions are limited to the oral cavity, PV sometimes may be managed successfully using only topical corticosteroids. However, it may not be possible to reduce the circulating Dsg autoantibody titers without systemic immunosuppression. The sustained high Dsg3 antibody level may cause "epitope spreading" and induce skin lesions. It may be prudent to determine post-treatment levels of Dsg using ELISA and, in consultation with the physician, recommend the addition of systemic therapy if Dsg3 levels remain elevated.

Using Desmoglein 1 and 3 Enzyme-linked Immunosorbent Assay as an Adjunct Diagnostic Tool for Pemphigus

Pemphigus is an acquired autoimmune intraepidermal blistering disease that is divided into 2 major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating anti-desmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. Recently, a novel commercial enzyme-linked immunosorbent assay (ELISA) against Dsg1 and Dsg3 has been established and found to be extremely sensitive and specific. To date, the usefulness of Dsg1 and Dsg3 ELISA in the diagnosis of pemphigus in the Taiwanese population has never been reported. Serum samples were obtained from 143 patients, including 20 patients with PV, 9 patients with PF, 72 patients with bullous pemphigoid, 1 patient with dermatitis herpetiformis and 41 patients with non-autoimmune blistering diseases. They were tested for anti-Dsg1 and anti-Dsg3 reactivity by ELISA. Seventeen of 20 PV sera (85%) exceeded the cut-off value of Dsg3 ELISA, and 9 of 9 PF sera (100%) exceeded the cut-off value of Dsg1 ELISA, while only 1 (0.88%) and 3 (2.6%) of 114 non-pemphigus sera exceeded the cut-off values of Dsg3 and Dsg1 ELISAs, respectively. Thus, the sensitivity and specificity of Dsg3 ELISA were 85% and 99.1%, while the sensitivity and specificity of Dsg1 ELISA were 100% and 97.4%, respectively. The correlation between ELISA scores and disease activity along the time course was examined in 6 PV patients and 1 PF patient, and the result was equivocal. Dsg1 and Dsg3 ELISAs provide a simple, highly sensitive and specific method that can serve as a useful adjunct tool for the initial diagnosis of pemphigus.

Clinical and serological follow-up studies of endemic pemphigus foliaceus (fogo selvagem) in Western Parana, Brazil (2001-2002)

Fogo selvagem (FS) has been described in several regions of Brazil, including the Western regions of the state of Parana. In 1990, Empinotti et al. reported case studies of 213 patients with FS that were collected from 1976 to 1988. The same author (J.C.E.) has observed that the frequency of cases in these regions of Parana has decreased. The purpose of this study was to clinically and serologically evaluate a small group of the patients originally reported in 1990 and compare data with a group of control individuals. These patients were treated at the onset of the disease with systemic steroids. Patients with FS, their unaffected relatives (n = 80) and genetically unrelated controls (n = 15) were identified during a field study from 1 May 2001 to 30 June 2002. Sera from nine patients with FS and six normal controls that were collected in the 1976-1988 evaluation were available for this study. The sera were tested by indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation using recombinant human desmoglein 1 (Dsg1). Only 16 of the originally identified 213 patients with FS were found during the field studies. Thirteen of the 16 patients were in clinical and serological remission; 20% of normal controls (19 of 95) were positive in the Dsg1 ELISA. The majority of these subjects (17 of 19) were genetically related to FS patients. Six normal controls that were positive in the Dsg1 ELISA in the original survey were found to be negative or weakly positive in this evaluation. The reduced frequency of positive serological markers of disease in patients and normal controls from Western Parana, as well as the absence of recurrent disease in previously identified patients, suggest that environmental antigenic stimulation of the population at risk may have decreased in recent years.

Early Detection and Successful Management of Oral Pemphigus Vulgaris: A Case Report

Pemphigus vulgaris (PV) is an autoimmune disease characterized by acantholysis in the epithelium. PV is often difficult to diagnose in the early stages, since the oral lesions are relatively nonspecific. We report on a case with a favorable outcome due to early diagnosis and effective treatment of oral lesions. A 53-year-old Japanese woman presented with a month-long history of painful gingiva. PV was diagnosed using clinical, histopathological, and direct immunofluorescence criteria 1 month after the first visit. Evaluation of the circulating autoantibody titers to desmoglein (Dsg)1 and Dsg3 was conducted by enzyme-linked immunosorbent assay (ELISA). Occlusive steroid therapy (OST) using a topical corticosteroid (0.1% triamcinolone acetonide) was provided for 8 weeks. After OST was completed, a buccal frenectomy was performed to eliminate localized toothbrushing trauma. There were no adverse effects on wound healing after the procedure. No oral PV lesions were detectable at the 9-month reevaluation, and the patient remains in complete remission. The Dsg1 ELISA was negative while the Dsg3 ELISA was indeterminate at the first visit. The Dsg1 ELISA was also negative at reevaluation, but Dsg3 ELISA reactivity had increased 9 months after completion of treatment. Large scale clinical trials will be required to validate the clinical benefits of the OST treatment regimen, and further research is necessary to determine the importance of ELISA antibody examination in long-term management of oral PV.

Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus

Background Pemphigus vulgaris (PV) shows autoimmune reaction against desmoglein 3 (Dsg3), whereas paraneoplastic pemphigus (PNP) shows autoimmune reaction against Dsg3 as well as numerous members of the plakin family. It has been demonstrated that in PV, dominant epitopes reside in N-terminal adhesive regions of Dsg3 and that the dominant IgG subclass against Dsg3 is IgG4. Objective We attempted to map conformational epitopes and analyze IgG subclass distribution against Dsg3 in PNP. Method Epitopes on Dsg3 for circulating IgG autoantibodies from PNP (n = 22) were studied with competition enzyme-linked immunosorbent assay (ELISA) using domain-swapped molecules between Dsg3 and Dsg1 and were compared with those for IgG autoantibodies from PV (n = 22). IgG subclass distribution was analyzed with PNP serum by Dsg3 ELISA (n = 17). Results Epitopes on Dsg3 in PNP were distributed more broadly through the extracellular domain of Dsg3 than were those in PV, although the N-terminal extracellular domains of Dsg3 were more frequently recognized than the C-terminal extracellular domains. IgG subclass in PNP was IgG1 and IgG2 dominant. Conclusion Autoimmune response against Dsg3 in PNP is more diversified than that in PV, a finding that suggests PNP and PV have different pathophysiologic mechanisms for triggering production of anti-Dsg3 IgG.