Role of BP230 autoantibodies in bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune disease associated with subepidermal blistering due to autoantibodies directed against BP180 and BP230. BP180 is currently considered as the major pathogenic autoantigen. However, previous clinical findings suggested that anti-BP230 autoantibodies alone can cause skin lesions in animal models and many BP patients. The characteristics of BP230 and the pathogenic roles of anti-BP230 antibodies have been proposed. First, at the molecular level, BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque and interacts with other constituents of hemidesmosomes. Second, the presence of BP230 autoantibodies may correlate with specific clinical features of BP. The immunoglobulin (Ig)G autoantibodies from BP patients react mainly against the C-terminus of BP230, while the IgE autoantibodies are still inconclusive. Third, in vivo, autoantibodies against BP230 involved in the disease may not only induce the inflammatory response but also impair the structural stability of hemidesmosomes. This article reviews recently published work about the role of BP230 and its antibodies, including IgG and IgE, aiming to find clues of its clinical association and lay the foundation for the research on the pathogenicity of antibodies against BP230.     

Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of Bullous Pemphigoid

Background

Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease associated with autoantibodies against BP180 and BP230. Enzyme-linked immunosorbent assay (ELISA) is a sensitive tool for the detection of immunoglobulin G (IgG) anti-BP180 and anti-BP230 autoantibodies.

Objective

The aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP.

Methods

We evaluated serum IgG levels of anti-BP180 and anti-BP230 autoantibodies in 47 BP patients, 16 epidermolysis bullosa aquisita patients, and 15 healthy volunteers using ELISA. Through retrospective review of the medical records, the clinical characteristics of BP including disease activity, duration, pruritus severity and peripheral blood eosinophil counts were assessed.

Results

The sensitivity of BP180 ELISA was 97.9%, BP230 ELISA 72.3%, and a combination of the two was 100%. The specificity of BP180 ELISA was 90.3%, BP230 ELISA 100%, and a combination of the two was 90.3%. BP180 ELISA scores showed strong associations with disease activity, pruritus severity, peripheral blood eosinophil counts, and disease duration, whereas BP230 ELISA scores did not.

Conclusion

BP180 and BP230 ELISAs are highly sensitive methods for the diagnosis of BP, and BP180 ELISA, in particular, is a sensitive tool for monitoring the disease activity of BP.     

Influence of intravenous immunoglobulin therapy on autoantibody titres to BP Ag1 and BP Ag2 in patients with bullous pemphigoid

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease, which is characterized by blisters on the skin. Autoantibodies to components of the basement membrane zone are usually observed in the sera of patients with BP. Autoantibodies to the bullous pemphigoid antigens (BP Ag1, 230-kDa desmoplakin protein, and BP Ag2, 180-kDa hemidesmosomal protein) are present in the sera of BP patients. OBJECTIVE: The objective of this study was to report the influence of intravenous immunoglobulin (IVIg) therapy on autoantibody titres to BP Ag1 and BP Ag2. METHODS: In this prospective study, we measured autoantibody titres to both BP Ag1 and BP Ag2, in 10 patients with severe BP, over a period of 18 consecutive months on each patient, using an immunoblot assay. RESULTS: Prior to the initiation of IVIg therapy, the sera of nine patients demonstrated the presence of high autoantibody titres to both BP Ag1 and BP Ag2. One patient had autoantibodies to BP Ag1 only. A statistically significant decline in the autoantibody titres to both BP Ag1 and BP Ag2 was observed after 3 months of receiving the first cycle of IVIg therapy. This gradual decline in autoantibody titres continued until patients were observed to have non-detectable titres to BP Ag1 after 11 months and to BP Ag2 after 10 months of receiving IVIg therapy. Once patients achieved non-detectable titres, these patients were considered to be in a serological remission. This serological remission was sustained for an additional 7 months of observation. CONCLUSION: Autoantibody titres to BP Ag1 and BP Ag2 can be used to monitor the serological response to treatment in patients with BP. Patients with severe BP who are treated with IVIg therapy, as described in our protocol, achieve a long-term serological remission.     

BP180NC16a与大疱性类天疱疮病情变化的关系

目的探讨大疱性类天疱疮(BP)患者外周血血清IIF滴度、BP180NC16a-ELISA指数与病情变化的相关性。方法监测12例以系统糖皮质激素治疗为主的泛发性BP患者不同时期病情变化及其相应的IIF滴度和BP180NC16a-ELISA指数,并对结果进行分析。结果IIF滴度与病情变化没有平行关系,BP180NC16a-ELISA指数与病情变化较平行。结论BP180NC16a-ELISA指数可作为BP病情的监测和调整治疗方案的重要参考。     

Autoantibodies to basement membrane proteins BP180 and BP230 are commonly detected in normal subjects by immunoblotting

Autoantibodies to basement membrane proteins BP180 and BP230 are characteristic of bullous pemphigoid and other subepidermal immunobullous disorders. These antibodies are, however, reported in other pruritic dermatoses, non-bullous disorders and non-cutaneous disease. Few studies have assessed basement membrane antibodies in normal subjects; antibody prevalence in this population is not clear. This study aims to examine basement membrane zone antibodies in normal middle-aged to elderly subjects. Sera from 61 healthy subjects (majority age 50–70 years) were assessed by immunoblot, indirect immunofluorescence and enzyme-linked immunosorbent assay. Ninety-one bullous pemphigoid patients acted as positive controls. Antigenic target, antibody class and titre were examined; sera binding BP180 were assessed for reactivity to the non-collagenous 16A (NC16A) domain. Thirty-six normal subjects (59%) had antibodies to either BP180 or BP230 on immunoblot analysis. BP180 was the commonest target antigen, detected in 35 subjects; binding to the immunodominant NC16A domain was not detected. Immunofluorescence was positive in three subjects. Of the bullous pemphigoid sera, 88% were positive on immunoblot or immunofluorescence; a higher frequency had antibodies against BP230. In conclusion, significant numbers of normal healthy subjects have circulating autoantibodies to basement membrane proteins, chiefly BP180 detectable by immunoblot, but these do not bind the NC16A domain.     

A case of pemphigoid gestationis with concurrent IgG antibodies to BP180, BP230 and type VII collagen

A 22‐year‐old primigravida had a pruritic, erythematous, bullous eruption on the skin during the 26th week of gestation. After delivery the eruption flared up. The diagnosis of pemphigoid gestationis was confirmed based on histopathological and immunofluorescence findings. The result of immunoblotting showed IgG autoantibodies which reacted against BP230 in epidermal extracts and 290 kDa type VII collagen in dermal extracts. The BP180 antibodies were also detected by an enzyme‐linked immunosorbent assay BP180NC16a diagnosis kit. Pulsed corticosteroid and cyclophosphamide resulted in a favourable response at the acute stage. The patient was cured in 2 years. The analysis of the patient's autoantibodies provides strong evidence for the involvement of epitope spreading in her autoimmune disease.     

Neue Aspekte zur Pathogenese des bullösen Pemphigoids

Bullous pemphigoid (BP) is a subepidermal blistering autoimmune disease of the elderly. Autoantibodies are directed against two hemidesmosomal proteins, designated BP180 and BP230. While BP230 localizes intracellularly and associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein with an extracellular domain consisting of approximately 1000 amino acids. The non-collagenous (NC) 16A domain, that encompasses 76 amino acids and localizes directly adjacent to the transmembrane region, has been identified as an immunodominant region of the BP180 ectodomain. In the majority of BP sera, circulating antibodies to BP180 NC16A are detected; their serum levels correlate with disease activity. Neonatal mice that are injected with rabbit anti-murine BP180 antibodies develop a BP-like subepidermal blistering disease demonstrating the biological importance of antibodies to BP180. The pathogenically relevant site on murine BP180 corresponds to a stretch of the NC16A domain on human BP180. In contrast to pemphigus, in BP, autoantibodies alone are not sufficient to induce blisters. In addition, complement activation, the infiltration of inflammatory cells and the release of proteases and various inflammatory mediators, including cytokines, are essential for lesion formation. In this review, we give an up-date on the pathogenesis of BP.     

Linear IgA dermatosis with IgA and IgG autoantibodies to the 180 kDa bullous pemphigoid antigen (BP180): evidence for a distinct subtype

BACKGROUND: Autoantibodies in linear immunoglobulin A (IgA) disease (LAD) are reported to be of IgA class and directed against a 97-120 kDa epidermal antigen. METHODS: We report a 39-year-old woman with clinical features of LAD and with circulating IgA and IgG autoantibodies to the 180 kDa bullous pemphigoid antigen (BP180). RESULTS: Histopathology of lesional skin revealed a subepidermal blister with mixed inflammatory cell infiltrate. Direct immunofluorescence of perilesional skin showed linear deposits of IgA along the dermal-epidermal junction. The antigen specificity of the patient's circulating antibodies was determined by Western blotting and enzyme-linked immunoabsorbent assay (ELISA) using various antigen sources, including cultured human keratinocytes, dermal protein lysates, and purified laminin-5, as well as proteins corresponding to BP180, the 230 kDa bullous pemphigoid antigen (BP230), laminin-5 subunits, and collagen IV alpha1-alpha6 chains. IgA and IgG antibodies in the patient's serum were directed against BP180, and no IgA or IgG reactivity was found against the other skin antigens. CONCLUSIONS: These data provide evidence for the presence of a subtype of LAD with dual IgA and IgG autoimmune response to BP180.     

Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid

OBJECTIVE: To investigate the possible correlation of levels of circulating anti-BP180 autoantibodies with disease activity in bullous pemphigoid (BP). DESIGN: Diagnostic study. SETTING: Regional referral center at a university dermatology department. PATIENTS: Fifteen patients with typical clinical, histologic, and immunofluorescence findings of BP who had not received prior systemic treatment. INTERVENTIONS: Initially, 6 consecutive patients with BP were treated with oral doxycycline and niacinamide. Subsequently, 9 consecutive patients with BP received a combination of oral dapsone and prednisolone. MAIN OUTCOME MEASURES: Disease activity, serum levels of autoantibodies to BP180, and titers of antibasement membrane zone autoantibodies were assayed before initiation of treatment and 4 and 8 weeks later. Reactivity to BP180 was analyzed by enzyme-linked immunosorbent assay using a recombinant form of BP180 NC16A. Titers of anti-basement membrane zone autoantibodies were assayed by indirect immunofluorescence on 1-mol/L sodium chloride-split human skin. RESULTS: In both treatment groups, disease activity correlated with serum levels of autoantibodies to BP180 NC16A (P = .004 [dapsone-prednisolone] and .007 [doxycycline-niacinamide]). No correlation was seen between disease activity and indirect immunofluorescence reactivity (P = .18 and .16, respectively). In patients receiving dapsone plus prednisolone, the dose of corticosteroids necessary to suppress new blister formation correlated with anti-BP180 reactivity (P = .002). CONCLUSIONS: In contrast to indirect immunofluorescence reactivity that reflects reactivity to both BP 180 and BP230, serum levels of autoantibodies to BP180 correlate with disease activity in BP. Assaying reactivity to BP180 should be a helpful guide for the therapeutic management of patients with this disease. Our results underline the pathogenic relevance of autoantibodies to human BP180.     

IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses

Background  Pruritic dermatoses of the elderly often pose a diagnostic and therapeutic challenge. Specifically, a prodromal phase of bullous pemphigoid (BP) has to be considered in patients with pruritic lesions of polymorphic appearance. These conditions frequently do not fulfil all the clinical, histological and immunopathological criteria for establishing the diagnosis of BP.
Objectives  To investigate IgG reactivity against the autoantigens of BP, BP180 and BP230, by enzyme-linked immunosorbent assay, in elderly patients affected with various pruritic disorders who had never experienced clinically apparent blisters.
Methods  The sera of 15 elderly patients with pruritic disorders (group I) were tested for IgG reactivity against BP180 and BP230. Also included were 30 patients with full-blown BP (group II) and 25 age-matched patients with immediate-type allergic reactions (group III).
Results  Thirty-three per cent of the patients with pruritic disorders (group I) showed IgG against BP230 and/or BP180: four of 15 patients had IgG against BP230 while two of the 15 group I patients were BP180 reactive. All the BP sera (group II) showed IgG reactivity against BP180 and/or BP230. Notably, two of 25 control sera (group III) showed IgG reactivity against either BP180 or BP230.
Conclusions  The present findings suggest that IgG reactivity against BP230 (i.e. the COOH terminus), and to a lesser extent against BP180, is a common finding in pruritic disorders of the elderly with a wide clinical spectrum. IgG-mediated autoimmunity against the intracellular BP230 may facilitate a chronic, inflammatory response eventually leading to full-blown BP which is presumably associated with IgG against BP180.     

Bullous pemphigoid: from the clinic to the bench

Bullous pemphigoid (BP) constitutes the most frequent autoimmune subepidermal blistering disease. It is associated with autoantibodies directed against the BP antigens 180 (BP180, BPAG2) and BP230 (BPAG1-e). The pathogenicity of anti-BP180 antibodies has been convincingly demonstrated in animal models. The clinical features of BP are extremely polymorphous. The diagnosis of BP critically relies on immunopathologic findings. The recent development of novel enzyme-linked immunosorbent assays has allowed the detection of circulating autoantibodies with relatively high sensitivity and specificity. Although potent topical steroids have emerged in the past decade as first-line treatment of BP, management of the disease may be challenging.     

Autoantibodies to the extracellular and intracellular domain of bullous pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong predominantly to the IgG1 and IgG4 subclasses

BACKGROUND: Autoantibodies to the extracellular domain (ECD) of bullous pemphigoid (BP) antigen 180 (BP180) are thought to play a crucial part in the pathophysiology of BP. OBJECTIVES: As the various IgG subclasses have different biological properties, we have sought to assess the relative isotype distribution of IgG to BP180 and their reactivity against the ECD and intracellular domain (ICD) of BP180. METHODS: The reactivity of 27 sera from patients with BP was assayed by immunoblotting against recombinant proteins covering the ECD and ICD of BP180. RESULTS: Twenty-seven (100%) and 21 (77%) of 27 BP sera, respectively, contained IgG1 and IgG4 autoantibodies binding to the ECD of BP180. Fourteen (82%) and six (35%) of the 17 BP sera that were reactive with the ICD of BP180 had autoantibodies of the IgG1 and IgG4 subclass, respectively. The profile of the isotype restriction appeared to be similar when the response to the ECD vs. that to the ICD was compared. IgG2 and IgG3 reactivity with BP180 was found less frequently. Patients with BP of longer duration showed a tendency to have, in addition to IgG1, an IgG4 response. CONCLUSIONS: Consistent with prior evidence indicating that subepidermal blister formation in BP is dependent upon complement activation, the frequent finding of complement-fixing IgG1 autoantibodies to both the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings provide new insights relevant for our understanding of the immune response to BP180, the putative key autoantigen in BP.     

Childhood bullous pemphigoid: clinical and immunological findings in a series of 4 cases

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is rare in childhood. As in adult BP, antibodies against the 180-kDa antigen (BP180) seem to be involved in the pathogenesis of the disease, but, to date, only a small number of children with the disease have been examined immunologically. OBSERVATIONS: We report the cases of 4 infants with BP aged 5 to 12 months. All of them had involvement of the hands and feet, and they all achieved a complete remission in less than 6 months when treated with oral prednisolone stearoyl glycolate. Three patients could be examined using antigen characterization techniques. Autoantibodies against the NC16A domain of BP180 were found by immunoblot assay in all 3 and by enzyme-linked immunosorbent assay in 2 of them. Interestingly, although IgA autoantibodies were detected in only 1 of them by indirect immunofluorescence, all of them had IgA autoantibodies, and 2 of the 3 had IgG autoantibodies against NC16A as detected by immunoblot assay. One patient also had IgG autoantibodies against the carboxyterminal domain of BP180. CONCLUSIONS: IgA-specific antibodies against BP180 were detected in all our patients. These findings further raise the question about the relationship between BP and linear IgA bullous dermatosis, the most common autoimmune blistering disorder in children.     

Demonstration of epitope-spreading phenomena in bullous pemphigoid: results of a prospective multicenter study

Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period. Epitope-spreading (ES) events were detected in 17 of 35 BP patients (49%). They preferentially occurred in an early stage of the disease and were significantly related to disease severity at diagnosis. Moreover, in three patients, spreading of IgG reactivity to intracellular epitopes of BP180 and BP230 was preceded by recognition of the BP180 ectodomain. Finally, IgG reactivity with extracellular epitopes of BP180 and intracellular epitopes of BP230 correlated with the severity of BP in disease course. These findings support the idea that IgG recognition of the BP180 ectodomain is an early and crucial event in BP disease, followed by variable intra- and intermolecular ES events, which likely shape the individual course of BP.     

IgE autoantibodies against the intracellular domain of BP180

Background  Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. BP not only involves IgG-mediated neutrophil activation, leading to blistering, but also IgE-dependent activation of mast cells and basophils. While IgG and IgE autoantibodies target the extracellular noncollagenous (NC) 16A domain of BP180, little is known whether other BP180 regions are targeted by these antibody classes.
Objectives  To characterize IgE and IgG autoantibody binding to antigenic sites on the intracellular domain (ICD) of BP180 compared with BP180 NC16A.
Methods  IgE/IgG autoreactivity against recombinant BP180 ICD and NC16A was determined by immunoblotting of sera from 18 patients with BP and 10 controls.
Results  Total serum IgE was elevated in 16 of 18 BP sera. Most BP sera tested positive (15 of 18) to NC16A with both immunoglobulin classes. Additionally, 14 of 18 sera showed IgE reactivity with an epitope mapped to the ICD of BP180 (amino acid residues 103–266). Mapping of ICD antigenic sites revealed similar IgE and IgG reactivities for most regions except for greater IgE reactivity to amino acid residues 234–398 (11 of 18 BP sera) than IgG (five of 18). Control sera failed to display IgE reactivity to these antigens.
Conclusions  The results indicate that BP180 NC16A is not the only antigenic determinant of IgE autoantibodies in BP and that additional, novel epitopes exist on different regions of the ICD of BP180. The heterogeneous autoimmune response against BP180 suggests intramolecular epitope spreading during disease progression.     

BP230- and BP180-specific auto-antibodies in bullous pemphigoid

Bullous pemphigoid is a subepidermal blistering disease associated with auto-antibodies (auto-ab) to BP180 and BP230. We developed ELISAs utilizing baculovirus-encoded recombinant proteins of BP230 and BP180 and studied their diagnostic and prognostic values by assessing the profile of the auto-ab response in 127 patients with BP. 39 patients had focal involvement, whereas 88 had generalized disease; 51 individuals served as controls. The results indicate: (1) BP180 IgG reactivity was associated with an overall sensitivity of 0.953 and specificity of 0.940; (2) 105 of 127 BP patients also displayed BP230 auto-reactivity, the global diagnostic performance of which, however, was moderate compared to BP180-auto-reactivity (sensitivity 0.815 vs 0.953, specificity 0.648 vs 0.940); (3) 101 patients (79.5%) had concordant BP180 and BP230 reactivity; (4) the association between the presence of BP230 auto-reactivity and focal involvement was stronger than in generalized disease (odds ratio (OR) 17.7 vs 10.2), independently from BP180 auto-ab profile; (5) correlation of total IgG with IgG1 and IgG4 was variable for both BP180 and BP230. Collectively, the global diagnostic properties of the BP180-ELISA outperform those of the BP230-ELISA. Presence of BP230 auto-reactivity, however, supports the diagnosis of BP and might be indicative for the extent of the disease.     

Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of the BP180 antigen for sensitive and specific detection of pemphigoid autoantibodies

Bullous pemphigoid (BP) and pemphigoid gestationis (PG) are acquired autoimmune subepidermal blistering diseases characterized by autoantibodies against the hemidesmosomal proteins BP180/type XVII collagen and BP230. In the vast majority of BP and PG patients, these autoantibodies bind to epitopes clustered within the 16th non-collagenous domain of BP180. An ELISA system for the detection of these autoantibodies was developed and evaluated using 16th non-collagenous domain (NC16A) tetramers instead of monomers. In contrast to antigens fused to large proteins used in the past for the detection of autoantibodies against type XVII collagen, tetrameric antigen fragments bearing a small hexahistidine tag allow for high expression levels without the need to cleave off the fusion partner. Using tetrameric BP180 NC16A, positive reactions were found in 106 (89.8%) of 118 randomly selected BP sera and in all of 20 (100%) randomly selected PG sera, whereas only 2.2% of a large cohort of control subjects were positive in this assay, including patients with rheumatoid arthritis (two of 107), progressive systemic sclerosis (two of 50), systemic lupus erythematosus (one of 72), and healthy blood donors (10 of 494). Thus, the sensitivity and specificity of the new anti-tetrameric NC16A ELISA were 89.9% and 97.8% respectively. Levels of circulating autoantibodies against BP180 paralleled disease activity in the pemphigoid patients. In conclusion, the use of tetrameric NC16A in ELISA results in a sensitive and specific tool for diagnosis and monitoring of BP and PG.     

Relapse‐associated autoantibodies to BP180 in a patient with anti‐p200 pemphigoid

Anti‐p200 pemphigoid and bullous pemphigoid (BP) are autoimmune subepidermal blistering diseases characterized by autoantibodies to a 200‐kDa dermal antigen (p200) and two hemidesmosomal proteins (BP180 and BP230), respectively. We report a 70‐year‐old man with haemorrhagic blisters, widespread crusted erosions, and the immunopathological characteristics of anti‐p200 pemphigoid. Treatment with doxycycline, topical corticosteroids and immunoadsorption led to rapid clinical remission. However, 19 weeks later, a relapse occurred with generalized itchy urticarial erythema and tense blisters. At this time, both strong dermal and epidermal IgG staining was detected by indirect immunofluorescence microscopy on salt‐split skin, and autoantibodies against both p200 and the 16th noncollagenous (NC16A) domain of BP180 were found. Interestingly, the relapse was associated not only with the detection of autoantibodies to a second autoantigen (BP180), but also with an altered clinical phenotype. This case was a unique occasion to directly monitor the emergence of intermolecular epitope spreading during the course of an autoimmune bullous disorder.     

IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in Bullous pemphigoid: serum levels of these immunoglobulins reflect disease activity

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease associated with autoantibodies against the hemidesmosomal glycoprotein BP180. The noncollagenous (NC)16A domain of BP180 has recently been shown to harbor major antigenic sites recognized by BP sera. OBJECTIVE: The purpose of this study was to characterize the subclass distribution and fine specificities of autoantibodies to BP180 NC16A present in the circulation of patients with BP before, and during the course of, therapy for this disease. METHODS: Eighteen BP sera were analyzed by immunoblotting and enzyme-linked immunosorbent assay for the presence of IgG1, IgG2, IgG3, IgG4, and IgE reactive with various sites on the BP180 NC16A domain. The sera were collected before treatment was started and at 4- and 8-week time points after initiation of treatment. RESULTS: We identified IgG4 and IgE as the major immunoglobulins that preferentially react with two distinct epitopes (MCW-1 and MCW-2) within BP180 NC16A. Levels of these autoantibodies correlated with disease activity in BP. During the course of disease, no change was observed with regard to the immunoglobulin subclass predominantly reacting with BP180 NC16A or the specific epitopes within this domain. CONCLUSION: Our data demonstrate that remission of BP is paralleled by a decrease of serum levels of IgE and the different IgG subclasses reactive with BP180 NC16A.     

Circulating Eosinophil and Neutrophil Counts Correlate with Disease Severity in Bullous Pemphigoid

BackgroundBullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by tissue-bound and circulating autoantibodies directed against BP180 and/or BP230 antigens. Various inflammatory cells are involved in the development of blister in BP.ObjectiveThe aim of this study was to evaluate the correlation between peripheral leukocyte counts and BP severity.MethodsWe retrospectively included 60 patients with BP, who had not been treated with systemic steroid at the time of blood sampling. The patients were classified into two groups, those with admission history (admission group) and those without admission history (non-admission group). Disease severity was evaluated using three parameters: admission history, initial steroid dosage, and modified version of a pemphigus scoring system. We evaluated the correlation between peripheral leukocyte counts and disease severity measured by the three parameters.ResultsThe admission group showed a significant increase in disease severity measured by initial steroid dosage and severity score compared with the non-admission group. Additionally, the admission group had increased total leukocyte, eosinophil, and neutrophil counts. In the correlation study, the peripheral eosinophil and neutrophil counts showed positive correlation with BP severity evaluated by both initial steroid dosage and the pemphigus scoring system.ConclusionPeripheral eosinophil and neutrophil counts can be used as a marker in predicting disease severity in patients with BP.