Bullous Pemphigoid Disease Activity Research Articles

Bullous pemphigoid burden of disease, management and unmet therapeutic needs.

Bullous pemphigoid (BP) is an autoimmune blistering disease that can have a profound negative impact on quality of life. BP most often affects the elderly, a population with a high medical burden and special safety concerns. In this review, we outline the BP disease course, diagnosis, epidemiology and comorbidities, and describe tools commonly used to assess BP disease activity and severity and the impact of BP on health-related quality of life. We also outline biologic treatments currently under investigation for the treatment of BP and highlight the importance of considering safety when treating elderly patients.

IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not correlate with disease activity of bullous pemphigoid.

The correlation between IgE anti-BP180 NC16A autoantibody and disease activity of bullous pemphigoid (BP) remains disputable. To determine the levels of IgE anti-BP180 NC16A autoantibody and its clinical significance in untreated BP patients. IgG and IgE anti-BP180 NC16A autoantibody in serum and blister fluid samples of 34 untreated BP patients was detected by enzyme-linked immunosorbent assay (ELISA), and correlation with clinical and pathological features of BP were statistically analysed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean baseline level of IgG anti-BP180 NC16A autoantibody in serum and blister fluid samples of untreated BP patients was 75.3U/mL and 1.54U/mL, respectively (A450, cutoff: 0.126). IgE anti-BP180 NC16A autoantibody was positive in 21.9% serum and 14.7% blister fluid samples of untreated BP patients. IgE anti-BP180 NC16A autoantibody levels in serum samples positively correlated with those from blister fluid samples (r = 0.983, p < 0.05). However, IgE anti-BP180 NC16A autoantibody level in both serum and blister fluid samples of untreated BP patients did not correlate with IgG anti-BP180 NC16A autoantibody, age, extent of elevated peripheral blood eosinophils, BPDAI erosion/blister score, BPDAI urticaria/erythema score, BPDAI pruritus score, BPDAI without damage score, or BPDAI total score (all p > 0.05). No significant correlation was identified between disease activity and positive or negative anti-BP180 NC16A IgE autoantibody. Conclusion: IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not appear to correlate with disease activity of BP.

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are positively correlated with disease activity of bullous pemphigoid.

Bullous pemphigoid (BP) is a complex inflammatory process with elevated levels of autoantibodies, eosinophils, neutrophils, and various cytokines. Hematological inflammatory biomarkers can reflect inflammatory state in various diseases. Up to now, the correlations of hematological inflammatory biomarkers and disease activity of BP remain unknown. The purpose of this study was to clarify the associations between hematological inflammatory biomarkers and disease activity of BP. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR) and mean platelet volume (MPV) of 36 untreated BP patients and 45 age and gender matched healthy controls were detected by routine blood tests. The correlations between hematological inflammatory markers and clinical characteristics of BP were statistically analyzed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean levels of NLR, PLR, PNR and MPV in 36 untreated BP patients were 3.9, 157.9, 45.7 and 9.4fl, respectively. Increased NLR (p < 0.001), PLR (p < 0.01), and MPV (p < 0.001) but decreased PNR (p < 0.001) were observed in BP patients when compared with healthy controls. In BP patients, the levels of NLR were positively correlated to BPDAI Erosion/Blister Scores (p < 0.01); and the levels of NLR and PLR were both positively correlated to BPDAI without Damage Score (both p < 0.05) and BPDAI Total Score (both p < 0.05). No correlation was found in other statistical analyses between hematological inflammatory markers and clinical characteristics in BP patients involved in the present study. Therefore, NLR and PLR are positively correlated with disease activity of BP.

123 Anti-BP180, Pruritus, and Thymus and Activation-Regulated Chemokines as Surrogate Markers for Disease Activity in Bullous Pemphigoid

Bullous pemphigoid disease activity index (BPDAI) is the standard indicator of disease activity in bullous pemphigoid (BP). However, examining patients’ whole body is burdensome to both the patient and health care workers and is subjected to inter-examiner bias, hence the need to investigate other surrogate markers for BPDAI. The purpose of the study is to quantify and correlate candidate surrogate disease markers of BP namely visual analogue scale for pruritus (VAS-pruritus), thymus and activation-regulated chemokines (TARC), and anti-BP180 to bullous pemphigoid disease activity index (BPDAI).

Onychomadesis: A marker of disease activity in bullous pemphigoid?

Onychomadesis: A marker of disease activity in bullous pemphigoid?

Elevated levels of sCD48 are inversely correlated with markers of disease activity in bullous pemphigoid.

sCD48 is elevated in diseases characterized by IgE and eosinophilia. Thus, serum levels sCD48 were evaluated in relation to clinical characteristics of Bullous pemphigoid (BP) patients. sCD48 levels were determined by ELISA in sera from 26 patients with classic BP and 26 healthy controls. Disease severity scores, differential blood counts, and circulating autoantibody levels were obtained. A correlation analysis was performed to establish relationships between sCD48 and clinical and laboratory markers of disease severity. Overall, circulating levels of sCD48 were significantly elevated in BP patients; however, when stratified based on disease severity, patients with mild-moderate disease had higher levels of sCD48 than those with severe disease. A Spearman's correlation analysis identified an inverse relationship between sCD48 and disease activity, serum BP180 IgE and peripheral eosinophil numbers. Further studies are needed to determine the pathologic relevance of these findings.

Characteristic Pattern of IL-17RA, IL-17RB, and IL-17RC in Monocytes/Macrophages and Mast Cells From Patients With Bullous Pemphigoid.

Inflammation is largely implicated in bullous pemphigoid (BP), the most frequent skin auto-immune blistering disease. IL-17, essentially IL-17A/F, has been involved in blister formation through regulation of protease production, and its specific serum profile within BP was related to disease outcome. However, relationships between IL-17 family ligands and receptors are quite complex with six different IL-17 isoforms, and five different receptors. We here aimed at clarifying the contribution of the IL-17 axis in BP by characterizing not only the expression of IL-17 receptor (IL-17R) members within immune cells isolated from BP patients (PMNs, n = 9; T-lymphocytes, n = 10; and monocytes, n = 10) but also the expression of IL-17 isoforms in sera (n = 83), and blister fluid (n = 31) of BP patients. We showed that at diagnosis, IL-17RA and IL-17RC expression were significantly increased in monocytes isolated from BP patients as compared to those from control subjects (p = 0.006 and p = 0.016, respectively). Notably, both IL-17RA and IL-17RC mRNA expression remained elevated in BP monocytes at time of relapse. We further demonstrated a significant increase of all IL-17 isoforms tested in BP blister fluid compared with BP serum (IL-17A, p < 0.0001; IL-17A/F, p < 0.0001; IL-17B, p = 0.0023; IL-17C, p = 0.0022; IL-17E, p < 0.0001). Among all, IL-17B was the only cytokine for which a significant decreased concentration within blister fluid was observed in BP patients with severe disease compared to patients with moderate disease (p = 0.012). We further evidenced a significant negative correlation between IL-17B levels and blister/erosion BPDAI subscore (r = −0.52, p = 0.003). We finally identified mast cells as a potential target of IL-17B in lesional skin of BP patients. In conclusion, we showed here that IL-17RA and IL-17RC expression in monocyte was associated with disease activity and evidenced in situ a negative correlation between BP disease activity and IL-17B, whose effects could be mediated by IL-17RB expressed by mast cell in BP lesional skin.

Blister Fluid Induces MMP-9-Associated M2-Type Macrophages in Bullous Pemphigoid.

Bullous pemphigoid (BP) is a cutaneous autoimmune disease, characterized by an inflammatory cascade leading to blister formation. Although macrophages were shown to participate in BP pathophysiology, their role in the blister formation process still needs to be investigated. We here addressed the influence of serum and blister fluid (BF) from patients with BP on the polarization status of macrophages with regards to the metalloproteinase-9 (MMP-9) expression. We demonstrated that several markers related to the alternatively activated macrophage phenotype (M2) including IL-10, TARC, arginase, TNFα, and IL-1RA were meaningfully increased in BF of patients with BP. We further showed that BF, but not serum from patients with BP, significantly induced the expression of CD163, CD206, and IL-10 in BP monocyte-derived macrophages (MDMs). Notably IL-10 was the only cytokine to be correlated to the reference clinical score, BP disease activity index (BPDAI), especially to the inflammatory BPDAI subscore evaluating urticarial and erythematous skin lesions (r = 0.57, p = 0.0004). We also found elevated levels of MMP-9 to M2-type macrophages ex vivo and highlighted the presence of CD163+ MMP-9+ macrophages histologically, at skin lesional site. Finally, we showed that methylprednisolone reduced MMP-9 levels in MDMs without modifying the other M2 markers. All together these results strongly support the presence of M2-phenotype macrophages with pro-inflammatory properties susceptible to favor blister formation in BP.

BPDAI and ABSIS correlate with serum anti-BP180 NC16A IgG but not with anti-BP230 IgG in patients with bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease characterized by autoantibody production against BP180 and BP230. Two scoring systems have been validated for BP including: Bullous Pemphigoid Disease Area Index (BPDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). In this study, we investigated correlations between both scoring systems and either anti-BP180 NC16A or anti-BP230 values. BPDAI and ABSIS were used to measure disease activity in 95 BP patients at Razi Hospital in Tehran, Iran. ELISA was performed on patient sera to identify any significant relationship between anti-BP180 NC16A/anti-BP230 values and BP disease activity. The two scores showed a strong correlation (ρ = 0.73; p value < 0.0001). Anti-BP180 NC16A values correlated with BPDAI (ρ = 0.49, p value = 0.0001), ABSIS (ρ = 0.47, p value < 0.0001), and BPDAI-Pruritus scores (ρ = 0.29, p value < 0.005). There was a strong correlation between anti-BP180 NC16A values and the ABSIS Skin score (ρ = 0.58, p value < 0.0001), and a moderate correlation with erosion/blister BPDAI score (ρ = 0.48, p value < 0.001) and urticaria/erythema BPDAI score (ρ = 0.27, p value = 0.009). Anti-BP230 values did not demonstrate any relationship with either scores or their subcomponents. Both scoring systems demonstrated moderate validity. Mucosal components did not show any correlation with anti-BP antibodies and are disproportionately presented in both BP scoring tools.

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.

Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid.

Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = -0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of the disease, but not in the early stages of medication.

Paper-Based ELISA for the Detection of Autoimmune Antibodies in Body Fluid—The Case of Bullous Pemphigoid

Bullous pemphigoid (BP), a common autoimmune blistering disease, is increasing in incidence and conveys a high mortality. Detection of autoantibodies targeting the noncollagenous 16A (NC16A) domain of type XVII collagen using enzyme-linked immunosorbent assay (ELISA) has demonstrated high sensitivity and specificity for diagnosing BP. We have developed a rapid, low-cost, and widely applicable ELISA-based system to detect the NC16A autoimmune antibody and then diagnose and monitor BP disease activity using a piece of filter paper, a wax-printer, and NC16A antigens. Both sera and/or blister fluids from 14 untreated BP patients were analyzed. The control group included healthy volunteers and patients with other blistering disorders such as pemphigus vulgaris. In our established paper-based ELISA (P-ELISA) system, only 2 μL of serum or blister fluid and 70 min were required to detect anti-NC16A autoimmune antibodies. The relative color intensity was significantly higher in the BP group than in the control groups when using either serum (P < 0.05) or blister fluid (P < 0.001) specimens from BP patients. The results of P- ELISA were moderately correlated with the titer of the commercial ELISA kit (MBL, Japan) (rho = 0.5680, P = 0.0011). This newly developed system allows for rapid and convenient diagnosis and/or monitoring of BP disease activity.

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

BackgroundBullous 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.ObjectiveThe aim of this study was to evaluate the usefulness of ELISA for diagnosing and monitoring the disease activity of BP.MethodsWe 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.ResultsThe 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.ConclusionBP180 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.

Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid

Titres of circulating autoantibodies detected by indirect immunofluorescence (IIF) have been used for the diagnosis and evaluation of disease activity in bullous pemphigoid (BP). In BP, the major pathogenic epitope is known to be the non-collagenous extracellular domain (NC16A) of the 180-kDa transmembrane hemidesmosomal protein (BPAG2). Recently, an enzyme-linked immunosorbent assay (ELISA) kit using the NC16A domain recombinant protein (BP180 ELISA kit) has become commercially available to measure the quantities of pathogenic autoantibodies circulating in BP patients. To investigate the correlation of clinical severity and ELISA indices in BP. Fourteen patients with a typical form of BP and one refractory BP patient who died despite extensive treatment were included in this study. Antibody titres in sera from these patients were measured using BP180 ELISA kit and an analysis of ELISA indices with disease activity was performed. ELISA indices were significantly reduced after successful therapy, although IIF titres did not always show apparent correlations. In the patient with refractory BP, ELISA indices also showed a good correlation with disease course. ELISA indices measured using the BP180 ELISA kit were well correlated with the disease activity. This commercially available kit more closely followed disease activities than the IIF titres. The BP ELISA system may be a useful tool to evaluate the disease activity and to assess the effectiveness of the treatment of BP.

Circulating levels of soluble E-selectin, ICAM-1 and VCAM-1 in bullous pemphigoid during low-dose methotrexate therapy. A prospective study.

Soluble iso-forms of cellular adhesion molecules (sCAMs) have been described and reported to be elevated in various inflammatory diseases. Elevated levels of sE-selectin have recently been detected and found to correlate with the number of blisters in bullous pemphigoid (BP) during oral corticosteroid therapy. In this prospective study we analysed levels of sCAMs in 10 elderly BP patients during low-dose oral pulse methotrexate monotherapy. We used standardised ELISA kits for soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin on 65 sera from 10 patients and 19 controls. Results were correlated with clinical parameters. Before therapy, we found significant elevation of sE-selectin (P=0.004) and sVCAM-1 (P=0.002) but not of sICAM-1. sE-selectin levels decreased during the efficient therapy and correlated with the number of blisters. Our results further support the proposition that sE-selectin might be a future clinical and predictive tool; but whether the elevation of sVCAM-1 also might reflect the disease activity in BP needs more investigation. The findings also indicate that BP might be more a cellularly mediated disease where interactions of different adhesion molecules play a crucial role.

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. (J Am Acad Dermatol 2000;42:577-83.)

Increased serum levels of interleukin (IL)-5, IL-6 and IL-8 in bullous pemphigoid

Some cytokines have been suggested to take part in the blister formation in bullous pemphigoid (BP). However, the roles of the cytokines are only partly understood. To elucidate the involvement of cytokines in the immunological mechanisms in BP, we investigated the serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-13, soluble IL-2 receptor and soluble CD23 in patients with BP, and the correlation between cytokine levels and other clinical and laboratory data. Serum levels of these cytokines and soluble receptors were determined by enzyme-linked immunosorbent assay in 19 patients with BP and in 16 normal control subjects. Serum levels of IL-5 ( P < 0.0001), IL-6 ( P < 0.01) and IL-8 ( P < 0.05) were significantly higher in BP patients than in the control subjects. Other cytokines and soluble receptor levels were not significantly different. Serum levels of IL-6 ( P < 0.05) and IL-8 ( P < 0.05) were significantly decreased after treatment when skin lesions disappeared. These results suggest that serum levels of IL-6 and IL-8 could be indicators of disease activity of BP.

Serum levels of soluble CD23 in patients with bullous pemphigoid.

In this study, we tested the serum levels of soluble CD23 (sCD23) in 27 bullous pemphigoid (BP) patients and compared them with the disease activity. Soluble CD23 is the cleaved portion of the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) which has an affinity for IgE and regulates IgE synthesis. Although bullous pemphigoid (BP) is a subepidermal blistering disease characterized by IgG class autoantibodies against the basement membrane of stratified squamous epithelia, several IgE-related phenomena have been reported. Recently, we have shown that Fc epsilon RII-expressing and IgE-bearing cells are detectable in the lesional skin and concluded that an IgE-Fc epsilon RII/CD23 system may be involved in the pathogenesis of this disease. The serum level of sCD23 in BP patients was significantly higher than healthy controls (p < 0.01). In 11 out of 12 patients, the alteration of serum sCD23 levels correlated well with the disease activity. Thus the serum level of sCD23 is useful as a new parameter for assessing the level of disease activity in BP. High levels of sCD23 may represent part of an IgE-mediated immune reaction which may play a role in the pathogenesis of BP.