Recent advances in the study of the pathophysiology of pemphigus

Recent rapid advances in the basic research into pemphigus have provided many insights into its pathophysiology. In particular, a recently developed enzyme-linked immunosorbent assay (ELISA) for desmogleins 1 and 3 (Dsg1 and Dsg3), antigens for pemphigus foliaceus (PF) and pemphigus vulgaris (PV), respectively, has led to great progress in the diagnosis and classification of pemphigus, as well as in understanding its pathomechanisms. Studies with the anti-Dsg1 and anti-Dsg3 antibodies have indicated that there are two types of PV, the mucosal dominant type and the mucocutaneous type. The same ELISA has identified the antigens in pemphigus herpetiformis. The autoantigens detected by this ELISA correlate well with the clinical features in pemphigus patients in showing the shift between PV and PF. In addition, the Dsg compensation theory proposed by Stanley and Amagai can reasonably explain the different depths of skin lesions and the different occurrences of skin and oral mucosal lesions between PV and PF. Furthermore, a complicated profile of autoantigens in paraneoplastic pemphigus (PNP) has been indicated in various biochemical studies, and IgG anti-Dsg1 and anti-Dsg3 antibodies have been detected in serum from all the PNP patients by the above ELISA. On the other hand, serum from subcorneal pustular dermatosis type IgA pemphigus patients have been shown to react with Dsc1, another type of desmosomal cadherin, by a novel cDNA transfection method. In addition, IgA anti-Dsg1 and anti-Dsg3 antibodies have been detected in a few patients with IgA pemphigus by an ELISA for IgA antibodies. Various autoimmune bullous diseases, including several types of pemphigus, are the only diseases in which the pathogenic role of circulating autoantibodies has been confirmed using the newborn mouse animal model. Therefore, studies of the pathophysiology of pemphigus are extremely important as a paradigm for research into various types of autoimmune diseases in other fields.     

Three cases of transition from pemphigus vulgaris to pemphigus foliaceus confirmed by desmoglein ELISA

We report 3 cases of pemphigus vulgaris (PV) confirmed by histology and direct and indirect immunofluorescence that showed transition to pemphigus foliaceus (PF) 2-4 years from the time of disease onset. Desmoglein (Dsg) ELISA testing of the sera from these 3 patients in the later stages of their disease showed the presence of anti-Dsg1 antibodies and the absence of anti-Dsg3 antibodies. These patients were on prednisolone and immunosuppressives at the time the sera were tested, and it is unclear if the transition from PV to PF is a permanent one or whether it is due to preferential suppression of Dsg3 antibodies below a certain threshold. Previously reported cases of transition from PV to PF and PF to PV are summarized.     

71例天疱疮的棘层松解位置分析

目的 探讨天疱疮的棘层松解位置,为天疱疮出现不同位置棘层松解的表现提供解释.方法 收集43例寻常型天疱疮和28例落叶型天疱疮患者的临床资料、组织病理、免疫病理、天疱疮抗体指标值进行分析.结果 寻常型天疱疮中有35例棘层松解的位置发生在基底层上方,8例发生在表皮中上部,落叶型天疱疮中有25例棘层松解的位置发生在颗粒层、棘层上方,3例发生在表皮中下部,落叶型天疱疮患者抗Dsg1抗体指标较寻常型天疱疮患者显著升高(P=0.047),寻常型天疱疮棘层松解的位置发生在表皮中上部的患者抗Dsg1、3抗体指标值与棘层松解发生在基底层上方的患者相比有差异,但无统计学意义.结论 寻常型天疱疮及落叶型天疱疮患者组织病理中,棘层松解的位置可发生于表皮中上部、表皮中下部.棘层松解的位置可能与抗Dsg1抗体和抗Dsg3抗体指标值等相关.     

Cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus

Pemphigus is an autoimmune blistering disease of the skin, mucous membranes, or both. There are two main categories of pemphigus: pemphigus foliaceus (PF) and pemphigus vulgaris (PV). PV is further subdivided into mucosal dominant and mucocutaneous types, according to the extent of cutaneous lesions. These classes of pemphigus have distinct histopathologic and serologic findings, with most cases falling into these subtypes. We report 4 cases that clinically showed blisters and erosions in the skin only, without mucosal involvement. Histologic examination of cutaneous lesions demonstrated suprabasilar acantholysis, a typical finding for PV. These patients had predominant anti-desmoglein 1 (Dsg1) IgG autoantibodies as well as anti-Dsg3 IgG autoantibodies, as determined by enzyme-linked immunosorbent assay. The desmoglein compensation theory posits that this rare phenotype can be produced by pathogenically weak anti-Dsg3 IgG in the presence of potent anti-Dsg1 IgG autoantibodies. Thus, cutaneous type PV without apparent mucosal involvement is observed as a rare clinical and histologic expression of pemphigus. This expression can be a transient phenotype that may develop from, or evolve into, other subtypes of pemphigus.     

The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay

BACKGROUND: There are a number of reports of pemphigus with clinical shifting between pemphigus foliaceus (PF) and pemphigus vulgaris (PV). On the other hand, a novel enzyme-linked immunosorbent assay (ELISA) against recombinant baculoproteins of desmoglein 1 (Dsg1) (PF antigen) and Dsg3 (PV antigen) has been established and found to be extremely sensitive and specific. OBJECTIVES: To characterize the change in the antibody profiles in a series of pemphigus cases with mixed features of PF and PV by various methods, including the novel ELISA. Patients/methods Sera were obtained from eight cases undergoing a shift between PF and PV and three cases of coexistent PF and PV. The autoantigens were analysed by ELISA, as well as by immunofluorescence using normal human skin sections and immunoblotting using normal human epidermal extracts. RESULTS: The results of the ELISA, immunofluorescence and immunoblotting studies showed that the transition between PF and PV correlates well with the changes of autoantibodies against either Dsg1 or Dsg3. CONCLUSIONS: The clinical phenotype at each stage is defined by the anti-Dsg antibody profile in the serum of these pemphigus patients showing mixed features of PF and PV. In addition, ELISA using recombinant baculoproteins was particularly useful in distinguishing PF and PV.     

Clinical and immunological features of pemphigus relapse

Pemphigus is a potentially fatal blistering skin disease. It is an autoimmune disease, meaning that the body's immune system, which normally fights off disease, in this case attacks healthy cells. The main treatments for pemphigus are with drugs called corticosteroids or immunosuppressive agents. The goal of treatment is to reach remission, a point where there are no new lesions (affected areas of skin) with minimal or no therapy (medication). However, many patients experience several relapses, meaning that after a period of improvement, the disease then worsens again, and it is often difficult for them to achieve remission. This study, from Japan, aimed to learn more about the risk factors and clinical features (signs) of pemphigus relapse. The authors retrospectively reviewed the medical records of 42 pemphigus patients. 61.9% of cases experienced relapse, usually when a medicine called oral prednisolone was tapered to around 0.1mg/kg. In a type of pemphigus called mucocutaneous pemphigus vulgaris (mcPV), the initial doses of prednisolone were lower in cases with relapse than without relapse. At relapse, mcPV shifted to subtypes (phenotypes) called mucosal dominant PV (mPV, which mainly affects the mouth and not the skin) (40%), pemphigus foliaceus (PF, affecting the skin) (20%) or others (20%). In contrast, the relapsing mPV and PF had the same clinical phenotypes as the initial phenotypes. Looking at antibodies, which are produced by the immune system to help fight off disease, patients with both anti-Dsg1 and anti-Dsg3 antibodies to begin with, had recurrence with anti-Dsg3 antibodies alone (40%), with both anti-Dsg1 and Dsg3 antibodies (30%) or with anti-Dsg1 antibody alone (20%). In conclusion, when a patient with mcPV relapses, there can be changes in the phenotype of their disease, and the antibodies being produced. At least 1mg/kg/day of prednisolone, especially for mcPV cases, and prudent tapering around 0.1mg/kg may lead to better outcomes.     

Human leukocyte antigen genotypes and antibody profiles associated with familial pemphigus in Japanese

Previous population-based, genetic studies have shown that human leukocyte antigen (HLA) class II loci such as HLA-DR4 (DRB1*04) and HLA-DR14 (DRB1*14) alleles are consistently associated with the occurrence of pemphigus vulgaris (PV) in Japanese as well as other ethnic populations. Among PV-related HLA-DRB1 alleles (*0406, *1401, *1405, *1406) in Japan, HLA DRB1*1405 and DRB1*0406 were found to be associated with both PV and pemphigus foliaceus (PF) phenotypes. We report four familial cases of pemphigus in two unrelated families, together with analysis of their HLA-DR and -DQ alleles, and their antibody profiles. One family comprised a woman with PF and her mother with PV: both patients shared a HLA haplotype of A31(19), B54(22), CW1 and DRB1*1405. Another family included two sisters with PF and PV, respectively: both of these patients shared a DRB1*1405-DQA1*0104-DQB1*0503 haplotype. Clinicopathological and serological monitoring revealed that the elder sister with PF presented with a PV phenotype later, and gained anti-desmoglein (Dsg)3 antibodies in addition to having a low titer of anti-Dsg1 antibodies. Conversely, the younger sister with PV developed PF with only anti-Dsg1 antibody detected. These results indicate that an HLA-DRB1*1405 (DQB1*0503) haplotype may confer susceptibility to both PV and PF, and that genetic susceptibility alone is not always responsible for the clinical phenotype and autoantibody profile.     

天疱疮患者桥粒芯糖蛋白抗体水平和疾病活动度关系及变化规律分析

目的 研究56例天疱疮患者疾病严重程度和桥粒芯糖蛋白1（Dsg1）和桥粒芯糖蛋白3（Dsg3）酶联免疫吸附试验（ELISA）指数之间的关系,探讨Dsg ELISA指数在不同型别天疱疮中转归的规律。 方法 用ELISA测定36例寻常型天疱疮和20例落叶型天疱疮患者治疗前、病情缓解且糖皮质激素开始减量时、糖皮质激素减量至相当于初始量1/2时、维持治疗开始时以及随诊2年时体内Dsg1和Dsg3 ELISA指数。 结果 Dsg ELISA指数与天疱疮疾病活动度相关,在疾病缓解时,Dsg ELISA指数下降,与治疗前差异均有统计学意义（P < 0.01）。在患者病情稳定使用维持量糖皮质激素、疗程到2年时,落叶型天疱疮中10例（50%）、寻常型天疱疮中7例（19.4%）Dsg1 ELISA指数出现阴性,只有1例（2.7%）寻常型天疱疮患者Dsg3 ELISA指数阴性。 结论 Dsg ELISA指数和天疱疮患者疾病严重程度相关,可能是一种评估病情的有用指标,可对治疗的有效性作出评价。     

天疱疮发病机制的研究进展

天疱疮是自身免疫引起表皮棘层细胞松解导致的慢性复发性表皮内大疱性皮肤病,典型表现为红斑基础上的疱壁松弛性水疱、糜烂、尼氏征阳性.依据天疱疮的临床表现,分为寻常型、增殖型、落叶型和红斑型天疱疮.天疱疮主要的发病机制是患者存在针对角质形成细胞桥粒芯(糖)蛋白的自身抗体,但棘层松解的详细机制尚不清.近年来,随着对蛋白组学、免疫学和分子生物学技术的发展以及天疱疮发病机制研究的不断深入,发现天疱疮的发病机制中除传统的桥粒芯(糖)蛋白自身抗体外,非桥粒芯(糖)蛋白抗体因素也参与了棘层松解的形成,为天疱疮提供了新的潜在治疗靶位.     

Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune skin diseases caused by autoantibodies against desmoglein (Dsg) 3 and Dsg1. We have previously developed ELISAs using recombinant Dsg3 and Dsg1 expressed by baculovirus as a diagnostic tool for pemphigus. In this study, we determined the frequency of coexistence of IgA class as well as distribution of IgG subclass. Two out of 49 PV and PF sera tested had anti-Dsg1 IgA in addition to anti-Dsg1 IgG. Interestingly, one of them showed prominent pustular formation. Among IgG subclass, IgG4 was predominant and found in all of the 30 PV and 19 PF sera tested, followed by IgG1, detected in 25 out of 30 PV and 12 out of 19 PF sera. Even though IgG2 and IgG3 were detected in 13 and one PV and 6 and 4 PF sera, respectively, the ELISA titers had barely exceeded the cutoff value in most of the cases. There was no IgG subclass shift during the course of the disease in seven cases examined. These findings indicate that IgG4 subclass is the predominant autoantibodies in both PV and PF, while IgG1 is also frequently found.     

Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)

We report a patient with herpetiform pemphigus(HP)who showed reactivity only with pemphigus vulgaris(PV)antigen but not with pemphigus foliaceus(PF)antigen. Direct and indirect immuno- fluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid- separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV.in addition to PF, with unique clinical and histological features.     

Anti-desmoglein IgG autoantibodies in patients with pemphigus in remission

Background   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.
Objective   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.
Methods   Dsg ELISA was performed on serum samples of PV and PF patients taken during remission (lesion-free ≥ 3 months on ≤ 15 mg 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.
Results   When remission was defined as no eruption ≥ 3 months with ≤ 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 ≤ 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.
Conclusions   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.     

天疱疮患者病情与抗桥粒芯蛋白抗体水平的相关性研究

目的:研究天疱疮患者血清中抗桥粒芯蛋白(desmoglein,Dsg)1和抗Dsg3抗体水平与其皮肤、口腔黏膜损害严重程度的相关性,同时对间接免疫荧光(IIF)检测的天疱疮抗体滴度与治疗中使用皮质类固醇控制剂量的相关性进行分析。方法:采用酶联免疫吸附试验(ELISA)试剂盒测定55例天疱疮患者血清中抗Dsg1和抗Dsg3抗体水平。结果:抗Dsg1抗体水平与患者皮肤损害严重程度有显著相关性(P<0.01),抗Dsg3抗体水平与口腔黏膜损害严重程度有显著相关性(P<0.01)。天疱疮患者血清IIF滴度与抗Dsg1抗体水平相关(P<0.01),寻常型天疱疮患者IIF滴度与抗Dsg1和抗Dsg3抗体水平均有相关性(P分别<0.01和<0.05)。寻常型天疱疮患者皮质类固醇控制剂量与抗Dsg1抗体水平和IIF滴度显著相关(P<0.05)。结论:ELISA方法检测天疱疮患者抗Dsg1和抗Dsg3抗体对天疱疮的临床诊断、分型、衡量口腔黏膜和皮肤损害严重程度具有一定意义。     

The transition of pemphigus vulgaris into pemphigus foliaceus: a reflection of changing desmoglein 1 and 3 autoantibody levels in pemphigus vulgaris

The transition of pemphigus vulgaris (PV) into pemphigus foliaceus (PF) is rare and the immunological changes underlying this event are not well understood. We report a 44-year-old woman who presented with oral and cutaneous erosions typical of PV. Over a 9-year period, the clinical features evolved into those of PF. To examine whether quantitative changes in desmoglein (Dsg) antibodies were associated with this transition, Dsg1 and Dsg3 antibody levels were measured by enzyme-linked immunosorbent assay in 82 sequential serum samples collected over this period. At presentation, when the phenotype was PV with oral and cutaneous erosions, antibodies to both Dsg1 and Dsg3 were detected. The disappearance of oral involvement was associated with a decline in Dsg3 antibodies, which are now undetectable, while the development of more severe skin involvement was associated with rising Dsg1 antibody levels. These data strongly suggest that the change in clinical features is a reflection of qualitative and quantitative changes in antibody profile. It is not known whether the transition to PF is permanent or whether disease relapses in the future may be associated with the re-emergence of Dsg3 antibodies, oral ulceration and a PV phenotype.     

Prolonged clinical remission of patients with severe pemphigus upon rapid removal of desmoglein-reactive autoantibodies by immunoadsorption

BACKGROUND: In pemphigus, loss of epidermal adhesion is induced by binding of circulating autoantibodies to the desmosomal cadherins desmoglein 3 (Dsg3) in pemphigus vulgaris (PV) and desmoglein 1 (Dsg1) in pemphigus foliaceus (PF), respectively. Therapeutic removal of Dsg-reactive autoantibodies by immunoadsorption (IA) has been demonstrated to exert clinical remission of the disease. OBJECTIVES: The aim of this intervention study was to evaluate the efficacy and safety of the peptide-based Globaffin adsorber system in the treatment of severe pemphigus cases. PATIENTS AND METHODS: We applied IA in 4 PV and 2 PF patients with severe chronic disease resistant to conventional immunosuppressive therapy. IA was performed on 4 consecutive days, representing 1 treatment cycle, followed by a 4-week treatment-free interval. Serum samples for determining serum IgG and anti-Dsg1/Dsg3 IgG autoantibodies were drawn daily before and after IA, respectively. During follow-up, patients were examined carefully, and laboratory parameters were controlled monthly for up to 1 year. RESULTS: IA led to excellent clinical responses. Skin and mucosal lesions cleared almost completely within weeks. One IA cycle reduced anti-Dsg1 and anti-Dsg3 autoantibodies by an average of 50-70% as determined by ELISA. CONCLUSIONS: Using the Globaffin adsorber system, IA represents an effective and safe treatment opportunity in severe and therapy-resistant pemphigus.     

Usefulness of enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus

Pemphigus is an autoimmune blistering disease with two major subtypes, pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with pemphigus have circulating antidesmoglein (Dsg)1 and/or anti-Dsg3 IgG autoantibodies. We have previously developed enzyme-linked immunosorbent assays (ELISAs) using recombinant Dsg1 and Dsg3 expressed by baculovirus as a diagnostic tool for pemphigus. The purpose of this study was to evaluate the practical application of these ELISAs for clinical use with a large number of serum samples. We used 81 PV sera, 48 PF sera, 114 bullous pemphigoid (BP) sera, 124 collagen disease sera, nine sera of other non-pemphigus bullous diseases and 179 normal control sera. A cut-off value was determined by receiver-operating-characteristic plots. Forty-seven of 48 PF sera (97.9%) were positive in the Dsg1 ELISA and 79 of 81 PV sera (97.5%) were positive in the Dsg3 ELISA, while only two (1. 1%) and four (2.2%) of 179 normal sera were positive in Dsg1 and Dsg3 ELISAs, respectively. However, some disease control sera of BP and collagen diseases exceeded the cut-off value. Introduction of a grey zone helped to decrease the number of these false-positive sera. Furthermore, in three patients studied, the respective Dsg1 and Dsg3 ELISA scores showed parallel fluctuation with the disease activity along the time course. We conclude that Dsg1 and Dsg3 ELISAs provide a simple, sensitive and highly specific assay for the diagnosis of patients with PV and PF and that these ELISAs may be a valuable tool to monitor the disease activity. We also propose diagnostic criteria for pemphigus based on ELISA reactivity: if a serum is positive against Dsg3 it indicates a diagnosis of PV, regardless of reactivity against Dsg1; if a serum is negative for Dsg3 and positive for Dsg1, it indicates a diagnosis of PF.     

Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin

The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies. Regional variations were observed in the expression of all these antigens. The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp. This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp. These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus.     

Case of pemphigus foliaceus that shifted into pemphigus vulgaris after adrenal tumor resection

A 79-year-old Japanese woman visited our hospital on 6 May 2003, who had suffered from erythema and crusted vesicles located on the head, face and trunk. The eruptions first appeared in February 2003. Histopathological findings included blister formation spreading from just below the horny layers to the upper squamous layers, where acantholytic cells were observed. Direct immunofluorescence disclosed immunoglobulin G depositions in the epidermal intercellular spaces. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein (Dsg)1 autoantibodies (154 index value), but almost normal levels of anti-Dsg3 autoantibodies (8 index value in serum). The diagnosis at first was made as pemphigus foliaceus (PF). Topical use of corticosteroids alone could control the eruptions well. Systemic examinations on admission revealed a right adrenal tumor that had caused Cushing's syndrome. Its resection was performed on 24 July 2003. Histopathological diagnosis of the removed tumor was a functional adrenal adenoma. The symptoms had worsened after the resection. Topical use of corticosteroids alone could no longer control the symptoms. Additional p.o. medications of minocycline hydrochloride and nicotinic acid amides improved the symptoms to some extent. However, oral cavity erosions appeared in December 2004, and the titer of anti-Dsg3 autoantibodies in serum elevated, suggesting a transition from PF to pemphigus vulgaris (PV). p.o. administration of corticosteroids started, which improved the symptoms significantly. To date, there have been no reports of pemphigus complicated with an adrenal tumor that caused Cushing's syndrome in Japan. The present case is particularly interesting in that the symptoms became worse after the tumor resection and that the first diagnosis of PF shifted into PV after the operation.     

A Case of pemphigus foliaceus which occurred after five years of remission from pemphigus vulgaris

A 77-year-old Japanese female developed pemphigus foliaceus (PF) after 5 years of remission from pemphigus vulgaris (PV). The patient had painful erosions in her mouth and flaccid blisters of the skin and was diagnosed as having PV, which responded well to corticosteroid treatment. She was then free from any lesion of PV for 5 years with a low dose of corticosteroid. Then she developed scaly erythematous lesions on the skin and was diagnosed as suffering from PF. Enzyme-linked immunosorbent assay (ELISA) using recombinant desmoglein 1 (Dsg-1) and Dsg-3 revealed that she had anti-Dsg-3 IgG in the PV stage, no antibodies during remission and anti-Dsg-1 IgG in the PF stage. These findings indicate that the target antigen was shifted from Dsg-3 to Dsg-1 along with the phenotype after a 5-year interval in this patient.     

Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression

The coexistence of antidesmoglein 3 (Dsg3) and antidesmoglein 1 (Dsg1) autoantibodies is well described in patients with pemphigus vulgaris (PV); however, there is little evidence of sequential development of these two autoantibodies. Autoantibody responses to Dsg3 and Dsg1 were studied in seven PV patients over time by enzyme-linked immunosorbent assay, using baculovirus expressed recombinant fusion proteins. All patients had anti-Dsg3 IgG antibodies at presentation. Two patients developed anti-Dsg1 later in the course of the disease. The transition in autoantibody profile was associated with disease progression to generalized PV involving mucous membranes and skin in both patients; one patient initially presented with a predominantly mucosal phenotype, the other with herpetiform pemphigus-like features. These findings demonstrate that there is an extension of autoimmune response from anti-Dsg3 only to both anti-Dsg3 and anti-Dsg1 in some patients, which is associated with an alteration in clinical expression in PV.