Pathogenesis Of Bullous Pemphigoid Research Articles

A distinct cutaneous microbiota profile in autoimmune bullous disease patients.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease in Europe. As both the incidence of the disease and the relative proportion of the elderly population continue to rise, it represents a significant medical burden. Whereas some progress has been achieved in defining genetic risk factors for autoimmune blistering diseases, no environmental agent has been conclusively identified. Emerging evidence suggests that host immunity may influence the skin microbiota, while the latter modulates cutaneous immunity. Nevertheless, the relationship between skin microbial communities and autoimmune bullous disease has yet to be studied in humans. Here, we aim to characterise and compare the skin microbiome of patients with BP and healthy, age-matched controls at numerous body sites. Similar to what has been shown in healthy controls, the composition of skin microbiota in patients with BP appears to be very divergent and site specific. Microbial phylum abundances differ between perilesional sites of patients with BP and the same anatomic locations of control patients. A distinct cutaneous microbiota profile, which correlates with BP, further strengthens the significance of commensal-host interaction on our immune system. Moreover, these results raise the possibility that the cutaneous microbiome may contribute to the pathogenesis of BP, with important implications for the treatment of this disease.

TWEAK/Fn14 activation contributes to the pathogenesis of bullous pemphigoid

Abstract Background Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. Objectives To explore the potential role of TWEAK/Fn14 activation in the pathogenesis of BP. Methods Twenty-three patients with BP and twenty healthy donors were recruited. The levels of TWEAK were determined in sera and BP fluids. Immunohistochemistry was performed with skin tissues for the expression of TWEAK, Fn14, and BP180. HaCaT cells were cultured in vitro, and received TWEAK stimulation. Some cells were pretreated with siRNA transfection or specific inhibitors before such stimuli. Results Serum levels of TWEAK increased in sera from BP patients, and correlated positively with anti-BP180 IgG. By immunohistochemistry, both TWEAK and Fn14 were overexpressed in BP lesion. In vitro experiments showed that TWEAK stimuli reduced BP180 expression in HaCaT cells and inhibited adhesion of cells to the culture dish. Consistently, the transfection of Fn14 siRNA preserved BP180 and protected cells from losing adherence. Moreover, specific inhibitors of the ERK and NF-κB pathways partially abrogated effect of TWEAK on cells. Finally, By silencing ADAM17 with siRNA, we found that ADAM17 mediated TWEAK-induced BP180 suppression. Conclusion TWEAK contributes to the pathogenesis of BP by reducing BP180 expression and cellular adherence, involving the activation of ERK and NF-κB pathways. TWEAK may serve as a biomarker or therapeutic target of BP.

Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid

IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes. To develop reliable enzyme-linked immunosorbent assays (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features. We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amounts of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of the IgE ELISAs were statistically compared with various ELISAs and various clinical parameters, including our own severity scores and BP phenotypes. IgG adsorption generally showed no changes in sensitivity and specificity for IgE ELISAs, although slight cross-reactivity of anti-IgE secondary antibody to IgG and interference of excess amounts of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti-BP180 antibodies correlated with disease activity but IgG and IgE anti-BP230 autoantibodies did not. IgE anti-BP230 autoantibodies correlated with nodular phenotype but not erythematous phenotype. The results of this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti-BP180 autoantibodies seemed to be pathogenic, while an association between IgE autoantibodies and inflammatory BP phenotype was not indicated.

TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid

TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients. Invitro TWEAK stimuli reduced BP180 expression in HaCaT cells and inhibited the adhesion of cells to the culture dish. Consistently, the transfection of Fn14 small interfering RNA preserved BP180 and protected cells from losing adherence. Moreover, such effect of TWEAK correlated with activation of the extracellular signal-regulated kinase and NF-κB pathways and downstream ADAMs. By silencing ADAM17 with small interfering RNA, we showed that ADAM17 participated in TWEAK-induced BP180 loss. Therefore, TWEAK may contribute to the pathogenesis of BP by reducing BP180 expression and cellular adherence, involving the activation of ERK and NF-κB pathways. TWEAK may serve as a biomarker or therapeutic target of BP.

Dysregulation of mCD46 and sCD46 contribute to the pathogenesis of bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a. Otherwise, the level of mCD46 was decreased in lesions of BP patients, whereas the complement activation was enhanced. We also found that CD46 knockdown in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Importantly, exogenous CD46 blocked complement activation in both healthy skin sections and keratinocytes induced by exposure to pathogenic antibodies from BP patients. These data suggest that CD46 deficiency is an important factor in BP pathogenesis and that increasing CD46 levels might be an effective treatment for BP.

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab')2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP.

A multi-hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA-DQB1*03:01, a potential link between immune privileged antigen exposure and epitope spreading?

Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA-DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease. In our proposed multi-hit hypothesis, patients with underlying neuronal disease are exposed to previously sequestered self-antigen, most importantly BP180. Patients with the HLA-DQB1*03:01 allele show an increased T-cell avidity to several epitopes of BP180, particularly the BP180-NC16a domain. Thus, they have a genetic susceptibility to developing BP upon exposure to the target antigen. In a patient with dysregulation of Th1/Th2 balance, anergy is lost and T-cells are subsequently primed resulting in the development of functional autoimmunity against the BP180-NC16a domain leading to clinically overt disease.

Detection of C-X-C chemokine receptor type 5 and inducible costimulator in blister fluid of patients with bullous pemphigoid

Objective To detect levels of C-X-C chemokine receptor type 5 (CXCR5) and inducible costimulator (ICOS) in blister fluid of patients with bullous pemphigoid (BP), and to explore their significance in the pathogenesis of BP. Methods Blister fluid samples were collected from 15 patients with BP (experimental group) and 15 patients with second-degree burns (control group). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of CXCR5 and ICOS in the 2 groups. Results The level of CXCR5 was significantly higher in the experimental group than in the control group (219 ± 145.31 vs. 147 ± 23.83 ng/L, t = 4.577, P 0.05). Conclusion The expression of CXCR5 may be associated with the occurrence of BP, but further researches are needed to determine the relationship between ICOS and the occurrence of BP. Key words: Pemphigoid, bullous; Receptors, CXCR5; Inducible costimulator; Blister fluid

Correlation between IL36α and IL17 and Activity of the Disease in Selected Autoimmune Blistering Diseases.

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

Autoantibody serum levels and intensity of pruritus in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease characterised by immunoglobulin G (IgG) autoantibodies to BP180 and BP230 [1]. Autoantibodies against BP180 have proved to play a critical role in the pathogenesis of BP, whereas autoantibodies against BP230 are thought not to be involved [2, 3]. Pruritus represents an important symptom in BP. Several authors investigated the association between serum levels of autoantibodies and disease severity [1-8], however, only few studies evaluated [...]

058 Identification Th2 cell epitopes in NC16A domain on bullous pemphigoid

Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease characterized by autoantibodies directed against BP180-NC16A, a transmembrane protein of epidermal basal cells. In this study, we examined and mapped the fine specificity of T cell epitope to NC16A. As IL-4 secretion is a marker of Th2 antigen-specific activation, PBMCs from 43 BP patients were collected and tested for IL-4 cytokine responses to a complete panel of 22 overlapping peptides spanning the BP180-NC16A domain by ELISPOT assay. Results revealed that IL-4 responses were significantly stronger for three peptides, P14, P18 and P21, in 27 BP patients, which representative aa492 to aa513 in NC16A domain. Further, Flow cytometry and ELISA analysis showed that those three peptides were able to stimulated BP patient’s PBMCs proliferation, B cells activation, pathogenic autoantibodies production, and linearly associated with BP180 titer in BP patients. As other studies have reported, HLA class II regions are linked to BP susceptibility in the Caucasian and Japanese population. We analyzed HLA I/II allele types of 43 Chinese BP patients and 500 healthy controls and found that HLA-DQB1*0602/0202, DRB1*1201/0101/0403/1602 were associated with BP in Chinese Hans population. To further define HLA restriction of those three peptides, we employed HLA-DQ, HLA-DP and HLA-DR neutralizing antibody to blocking antigen presenting during ELISPOT assay. The data showed that HLA-DR antibody could completely block P21 induced IL-4 sections while HLA-DQ and HLA-DP antibody has no effect on this process, which indicated that HLA-DR was involved in the P21 induced antigen presentation process. The P14 and P18 peptides HLA restriction will be confirmed by further study. In conclusion, our research identified aa492 to aa513 as a specificity of T cell epitope to NC16A, those regions are HLA-DR restriction and have the ability to stimulated BP patient’s T cells proliferation, B cells activation and pathogenic autoantibodies production. This results may contribute to the understanding the pathogenesis of BP.

Serum levels of immunoglobulins G1 and G4 targeting the non-collagenous 16A domain of BP180 reflect bullous pemphigoid activity and predict bad prognosis.

Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease, and different immunoglobulin (Ig)G autoantibody subclasses may play different roles in the pathogenesis of BP. This study aims to evaluate the relationship between specific IgG subclasses and BP. Enzyme-linked immunoassays (ELISA) were developed to test the IgG subclasses targeting the non-collagenous 16A (NC16A) domain of BP180. A statistical analysis was carried out to assess the relationship of BP and IgG subclasses as well as other factors. The correlation coefficients between the ELISA scores for four IgG subclasses and disease severity scores were 0.586 for IgG, 0.441 for IgG1, 0.594 for IgG2, 0.345 for IgG3, and 0.448 for IgG4 before treatment. After treatment, the correlation coefficient was 0.376 for IgG, 0.522 for IgG1, 0.314 for IgG2, 0.582 for IgG3 and 0.503 for IgG4. Spearman's rank correlation coefficient was 0.801 for IgG1, 0.66 for IgG2, 0.575 for IgG3 and 0.463 for IgG4 between the ELISA scores of IgG subclasses and the disease severity score variation. The ELISA scores of IgG subclasses in patients with mucosal involvement were higher than those without. Survival analysis showed that sex, IgG1 and IgG4 were the independent predictors for BP. In conclusion, the serum levels of IgG1 and IgG4 targeting BP180NC16A were paralleled with disease severity in BP patients. IgG1 and IgG4 and sex were the independent prognostic factors for an early prognosis of BP.

Genetic pathogenesis of bullous pemphigoid: an update

Bullous pemphigoid (BP) is an autoimmune disease associated with heredity,environment,infection,drugs,physical factors,and so on,of which,genetic factors play an important role in the pathogenesis of this autoimmune disease.It has been shown that human leukocyte antigen (HLA) loci,especially human leukocyte antigen (HLA) class Ⅱ alleles,are related to BP.Both consistency and variety exist in susceptibility genes for BP among different regions.Moreover,it is likely that non-HLA candidate genes are involved in the pathogenesis of BP,such as cytokine genes,immunoglobulin variable-region heavy chain 3 (IGHV3) genes,Km genotype,and Fc gamma receptor genes.Large-scale studies are required to investigate into these candidate genes. Key words: Pemphigoid, bullous ; Genetics ; Genes

Omalizumab therapy for bullous pemphigoid

Bullous pemphigoid (BP) responds to a variety of immunosuppressive agents and usually controls, but does not cure, the disease. Omalizumab, Food and Drug Administration-approved for asthma, selectively suppresses the activity of IgE, an important immunoglobulin in the pathogenesis of BP. We wished to determine if systemic omalizumab would have a therapeutic effect in patients with BP. We treated 6 patients with BP using omalizumab and followed up their disease for up to 42 months. Although variable, 5 of the 6 patients with BP received therapeutic benefit from systemic omalizumab (the sixth terminated treatment because of intercurrent illness) with less use of other immunosuppressants, inhibition of new bullae, less pruritus, and dramatic decreases in eosinophil counts. None of the patients had untoward side effects from omalizumab. This was an open, uncontrolled study. Omalizumab neutralizes the activity of IgE in patients with BP and improves the control of their disease activity.

Serum soluble CD200 level was higher in patients with bullous pemphigoid during the active phase of the disease than for healthy individuals.

CD200 is a novel immunosuppressive molecule, existing both as cell membrane bound and as a soluble form in serum (sCD200), which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was found in serum and blister fluid in a patient with bullous pemphigoid and that anti-IgE therapy impacted those levels. We therefore planned this study to evaluate the soluble serum CD200 levels of bullous pemphigoid patients and compare it with that of healthy controls. We also analysed the association between the sCD200 levels and the clinical severity of the disease in bullous pemphigoid patients. We investigated 5 consecutive patients with bullous pemphigoid, and 15 healthy controls were included in this study. Assessment of clinical examination and measurement of laboratory investigation were performed on the same day. Bullous pemphigoid patients were also assessed for Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Concentrations of anti-BP180 and soluble CD200 in the serum samples were quantified using ELISA kits. The serum soluble CD200 level was observed to be statistically significantly higher in patients with BP (77.6 +/- 15.7 pg/mL) compared with healthy controls (26.1 +/- 6.7 pg/mL), (p < 0.001). Nevertheless, there was no statistically significant correlation between serum soluble CD200 levels and clinical severity scores and Anti-BP180 values (p = 0.402, p = 0.395, respectively). However, there was a statistically significant correlation between ABSIS and Anti-BP180 levels in patients with BP (p = 0.036). CD200 might play a role in the immune response in the pathogenesis of bullous pemphigoid. However, we do not know the exact mechanism of CD200 in the disease initiation and/or progression.

Follicular Helper T Cells (Tfh) and IL-21 Involvement in the Pathogenesis of Bullous Pemphigoid

The pathogenesis of bullous pemphigoid (BP) is characterized by the T cell-dependent production of autoantibodies. Recent studies have indicated that follicular T helper cells (Tfh), the key modulator of B cell activation and autoantibody production, are critical in the development of several autoimmune diseases. Tfh cells perform their functions via IL-21, their hallmark cytokine. In the present study, the frequencies of Tfh cells were investigated in the peripheral blood samples of BP patients to evaluate whether Tfh cells involve in this clinical entity. Significantly higher Tfh cell counts were observed in the peripheral blood of BP patients than those in healthy controls (median: 11.25% vs. 4.95%, respectively; P<0.001). Additionally, the serum IL-21 levels in BP patients were higher than those of the healthy controls (median: 103.98 pg/mL vs 46.77 pg/mL, respectively; P<0.001). The frequencies of Tfh cells and IL-21 levels were both positively correlated with anti-BP180-NC16A autoantibody titers (R = 0.712, P<0.01 and R = 0.578, P = 0.030, respectively). After effective therapy, the frequencies of Tfh cells as well as the serum IL-21 levels in BP patients decreased along with clinical improvement. Most importantly, Tfh depleted CD4+ T cells and anti-IL-21 neutralization antibody could inhibit the T cell-induced B cell activation and secretion of BP autoantibody in vitro. Those results suggest that Tfh cells play an important role in autoantibody production and are involved in the pathogenesis of BP.

Follicular helper T cells in peripheral blood of patients with pemphigus and bullous pemphigoid

Objective To explore the roles of follicular helper T cells (Tfh) in the pathogenesis of pemphigus and bullous pemphigoid (BP).Methods Venous blood was collected from 20 patients (including 10 cases of pemphigus and 10 cases of BP) and 20 age- and sex-matched normal human controls.Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of serum interleukin (IL)-21 and anti-BP180-NC16A antibody,and flow cytometry to detect the percentage of Tfh in peripheral blood mononuclear cells (PBMCs).The relationship of anti-BP180-NC16A antibody titer to Tfh and IL-21 levels was assessed by linear correlation analysis.Results The serum IL-21 level and Tfh percentage in PBMCs were significantly higher in patients with pemphigus than in the normal controls (95.33 ± 33.69 vs.54.50 ± 18.13 pg/ml,t =3.38,P＜ 0.01;12.08％ ± 4.74％ vs.6.15％ ± 1.62％,t =3.74,P ＜ 0.01),and higher in patients with BP than in the normal controls ( 106.70 ± 44.91 vs.55.37 ± 15.89 pg/ml,t =3.41,P ＜ 0.01; 11.85％ ± 3.14％ vs.6.03％ ± 1.74％,t =5.13,P ＜ 0.01 ).The titer of anti-BP180-NC 16A antibody was positively correlated with the percentage of Tfh (r =0.67,P＜ 0.05) and serum level of IL-21 (r=0.77,P＜ 0.01) in patients with BP.Conclusions There is a significant increase in the percentage of Tfh and serum level of IL-21 in patients with pemphigus and BP,hinting a certain role of Tfh and IL-21 in the pathogenesis of pemphigus and BP. Key words: Pemphigus; Pemphigoid,bullous; T-lymphocytes,helper-inducer,Intedeukin-21; Autoantibodies

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid

Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.

Blistering insights into the pathogenesis of bullous pemphigoid

Blistering insights into the pathogenesis of bullous pemphigoid

Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid

Eosinophils contribute to the pathogenesis of bullous pemphigoid (BP) by secretion of proinflammatory cytokines and proteases. Trafficking of eosinophils into tissue in animal models and asthma depends on interleukin-5 and a family of chemokines named eotaxins, comprising CCL11, CCL24 and CCL26. Up-regulation of CCL11 has been described in BP, but the expression of the other two members of the eotaxin-family, CCL24 and CCL26, has not been investigated. In addition to these chemokines, expression of adhesion molecules associated with eosinophil migration to the skin should be analysed. We demonstrate that similar to CCL11, the concentration of CCL26 was up-regulated in serum and blister fluid of BP patients. In contrast, the concentration of CCL24 was not elevated in sera and blister fluid of the same BP patients. In lesional skin, CCL11 and CCL26 were detected in epidermis and dermis by immunohistochemistry. In contrast to CCL11, CCL26 was expressed strongly by endothelial cells. In line with these findings, eosinophils represented the dominating cell population in BP lesional skin outnumbering other leucocytes. The percentage of eosinophils expressing very late antigen (VLA): VLA-4 (CD49d) and CD11c correlated with their quantity in tissue. Macrophage antigen (MAC)-1 (CD11b/CD18) was expressed constitutively by tissue eosinophils. In conclusion, these data link the up-regulation of the eosinophil chemotactic factor CCL26 in BP to the lesional accumulation of activated eosinophils in the skin. Thereby they broaden the understanding of BP pathogenesis and might indicate new options for therapeutic intervention.