Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C‐terminal domain and laminin gamma‐1

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180‐kDa bullous pemphigoid antigen (BP180) non‐collagenous 16a (NC16a) domain or anti‐laminin‐γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C‐terminal domain and laminin‐γ1. A 64‐year‐old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl‐split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C‐terminal domain and 200‐kDa laminin‐γ1 in normal human dermal extract.     

Linear arrangement of neutrophils along the Basal layer in bullous pemphigoid: a unique histological finding

Bullous pemphigoid is an inflammatory autoimmune subepidermal bullous disease with distinct immunohistological features. We report an unusual case of a 59-year-old woman with a bullous eruption whose lesional skin biopsy showed a subepidermal blister with a linear arrangement of neutrophils, mimicking linear IgA bullous dermatosis. However, direct immunofluorescence studies demonstrated IgG and C3 linear deposition along the basement membrane zone, compatible with bullous pemphigoid. We suggest that bullous pemphigoid should therefore be considered in the differential diagnosis of neutrophil-rich subepidermal bullous diseases along with dermatitis herpetiformis and linear IgA.     

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.     

Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180.

Lichen planus pemphigoides is an autoimmune subepidermal blistering disease. The finding of immunoglobulin G antibodies directed against the basement membrane zone differentiates it from bullous lichen planus. The aim of this study was to identify the target antigen of lichen planus pemphigoides autoantibodies. Sera from lichen planus pemphigoides patients (n = 4) stained the epidermal side of NaCl-split human skin in a pattern indistinguishable from that produced by bullous pemphigoid sera. In bullous pemphigoid, the autoimmune response is directed against BP180, a hemidesmosomal transmembrane collagenous glycoprotein. We previously demonstrated that bullous pemphigoid sera predominantly react with a set of four epitopes (MCW-0 through MCW-3) clustered within a 45 amino acid stretch of the major noncollagenous extracellular domain (NC16A) of BP180. By immunoblotting and enzyme-linked immunosorbent assay, lichen planus pemphigoides sera were also strongly reactive with recombinant bullous pemphigoid 180 NC16A. The lichen planus pemphigoides epitopes were further mapped using a series of overlapping recombinant segments of the NC16A domain. All lichen planus pemphigoides sera reacted with amino acids 46-59 of domain NC16A, a protein segment that was previously shown to be unreactive with bullous pemphigoid sera. Two lichen planus pemphigoides sera, in addition, reacted with the immunodominant antigenic region associated with bullous pemphigoid. In conclusion, there are now five bullous diseases that are associated with an autoimmune response to BP180: bullous pemphigoid; pemphigoid/herpes gestationis; cicatricial pemphigoid; linear immunoglobulin A disease; and lichen planus pemphigoides. In addition, we have identified a novel epitope within the BP180 NC16A domain, designated MCW-4, that appears to be uniquely recognized by sera from patients with lichen planus pemphigoides.     

IgG autoantibodies from bullous pemphigoid patients recognize multiple antigenic reactive sites located predominantly within the B and C subdomains of the COOH-terminus of BP230

Bullous pemphigoid is a subepidermal bullous disorder characterized by an autoantibody response against the bullous pemphigoid antigen 230 (BP230) and the bullous pemphigoid antigen 180 (BP180), a cytoplasmic component and a transmembrane component, respectively, of hemidesmosomes. Although immunodominant sequences within the extracellular domain of BP180 have been identified, characterization of the antigenic sites on BP230 is still incomplete. To identify autoantibody-reactive sites on BP230 and to examine whether the targeted regions are contained within functionally important domains, recombinant fragments encompassing almost the entire BP230 were used to assess the reactivity of 25 bullous pemphigoid sera by immunoblotting. Our results demonstrate that (i) the region bearing the B and C subdomains of the COOH-terminus of BP230 contains immunodominant sequences recognized by the majority of bullous pemphigoid sera; (ii) additional autoantibody- reactive sites are present over extended regions of the NH2-terminal half of BP230 without evidence for antigenic cross-reactivity between the NH2- and COOH-termini of BP230; and, finally, (iii) autoantibodies reacting with the BP230 tail predominantly belong to the IgG4 and IgG1 subclasses, suggesting that both autoreactive TH2 and autoreactive TH1 cells regulate the autoantibody response to immunodominant sequences of BP230. As the COOH- terminus of BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque, whereas its NH2-terminus contains sequences important for its interaction with other constituents of hemidesmosomes, autoantibodies to BP230 might precipitate subepidermal blister formation and perpetuate the disease not only by eliciting an inflammatory reaction but also by interfering with the function of BP230 and thus the stability of hemidesmosomes.     

Two cases of subepidermal blistering disease with anti-p200 or 180-kD bullous pemphigoid antigen associated with psoriasis

We describe two patients with psoriasis vulgaris who subsequently developed a subepidermal blistering disease which disclosed IgG and C3 at the basement membrane zone in direct immunofluorescence. The first case was a 75-year-old Japanese man with herpetiform lesions. Histopathology showed neutrophil infiltration. IgG antibodies bound to the dermal side of the salt-split skin. Immunoblot analysis identified a 200-kD antigen in dermal extracts. The second case was a 70-year-old Japanese man. Histopathology showed eosinophil infiltration. IgG antibodies bound to the epidermal side of salt-split skin. Immunoblot analysis identified a 180-kD bullous pemphigoid (BP) antigen in epidermal extracts. We review the clinical and pathological features of psoriatic patients who presented a subepidermal blistering disease in which antigens were detected by immunoblot analysis; i.e., anti-p200 pemphigoid (14 cases) or BP (12 cases). There were few distinct clinical differences between two diseases. However, neutrophils were predominant in anti-p200 pemphigoid, while eosinophils were predominant in BP. After blister formation, ciclosporin was used effectively in addition to systemic steroids in the treatment of anti-p200 pemphigoid. On the other hand, ciclosporin was not used in the treatment of BP with psoriasis.     

Blister fluid for the diagnosis of subepidermal immunobullous diseases: a comparative study of basement membrane zone autoantibodies detected in blister fluid and serum

The subepidermal immunobullous diseases bullous pemphigoid (BP), cicatricial pemphigoid (CP), pemphigoid gestationis (PG) and linear IgA disease (LAD) are characterized by circulating and in vivo deposition of antibodies to antigens in the cutaneous basement membrane zone (BMZ). Indirect immunofluorescence (IMF) of serum is a routine diagnostic test to detect circulating BMZ antibodies in these diseases. We have compared the titres of IgG and IgA and their subclasses, also of IgM and IgE BMZ antibodies in serum and aspirated blister fluid in 35 adult patients with subepidermal immunobullous diseases: BP ( n  = 30), PG ( n  = 2), CP ( n  = 1), and LAD ( n  = 2), by indirect IMF on intact and salt-split skin. The antibody titre in blister fluid was the same or one dilution less than serum in most cases and there was no significant difference between these results ( P  > 0.05). IgG1 and IgG4 were the predominant subclasses in both blister fluid and serum in BP. Indirect IMF of serum and blister fluid was also carried out on trypsinized epidermal cells in a subgroup of patients with BP ( n  = 19). Typical polar fluorescence was obtained in all 14 cases which had positive indirect IMF on intact and split skin. Our findings demonstrate that blister fluid can be used as an alternative to serum for indirect IMF in subepidermal immunobullous diseases. This avoids the need for venesection and has a practical application in children and those with poor venous access.     

Increased levels of immunoreactive leukotriene B4 in blister fluids of bullous pemphigoid patients and effects of a selective 5-lipoxygenase inhibitor on experimental skin lesions

The immunoreactive leukotriene B4 (i-LTB4) and i-LTC4 content in the blister fluids of patients with bullous pemphigoid (BP) was determined by radioimmunoassay. Their amounts significantly exceeded those noted in superficial dermal burn patients and those in the fluids of suction blisters produced on normal human skin. When either BP blister fluids or BP-IgG from the patient sera were injected into guinea pig skin, neutrophil and eosinophil infiltrates were produced in the dermis. In addition, the dermis was noted to undergo marked edematous change. A single oral administration of a selective inhibitor of 5-lipoxygenase 1 hr before the intracutaneous injection of BP-IgG was found to significantly inhibit cell infiltrates. Furthermore, the inhibitor partly suppressed dermal epidermal separation. On the basis of these results. LTB4 and LTC4 appear to be generated in the skin lesions of BP, the former attracting granulocytes to the dermis and the latter, causing exudation.     

Localized Bullous Pemphigoid: Report of a Case with an Immunofluorescence and Electron Microscopical Studies on the Lesional Distribution of 180-KD Bullous Pemphigoid Antigen, β4 Integrin,and Type VII Collagen

A 67-year-old woman with a left-sided hemiplegia had localized bullous pemphigoid demonstrating typical clinical lesions on the left pretibial skin and the radial-side skin of the right forearm. The histology showed a subepidermal blister with extensive hyperkeratosis, hypergranulosis, and acanthosis. Direct immunofluorescence revealed distinct linear deposits of IgG and C3 at the dermo-epidermal junction in the perilesional skin and in the roof of the blisters, but few deposits in nonlesional skin. Electron microscopy revealed separation in the lamina lucida. Indirect immunofluorescence of type VII collagen showed its localization in the blister floor. The distribution of the 180-KD bullous pemphigoid antigen (BPA) and β4 integrin, hemidesmosomal transmembrane proteins, were studied in the lesional skin by indirect immunofluorescence. Both 180-KD BPA and β4 integrin were localized in the blister roof. By immunoelectron microscopy, β4 integrin was detected in small groups on the cell surface facing the blister cavity. Since the epitope of the monoclonal antibody to 180-KD BPA used here is known to be localized at a distance of 20 to 50 nm from the membrane surface and this epitope retained in the blister roof, it appears that the blister was produced in the deep lamina lucida. The lesions were cleared with topical 0.05% clobetasole propionate ointment.     

The distribution of α6β4 integrins in lesional and non-lesional skin in bullous pemphigoid

The alpha 6 beta 4 integrin is associated ultrastructurally with the hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen (BPA), suggesting an important role in adhesion of epidermal cells to the basement membrane. Using an immunofluorescence technique with chain-specific monoclonal antibodies to the alpha and beta subunits we have investigated the distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin (uninvolved, perilesional and lesional) [n = 11]). The findings have been compared with other types of subepidermal blisters and with normal skin split by chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4 integrin was compared with that of bullous pemphigoid antigen (BPA) and with other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV, collagen type VII and the BM600 antigen. In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters, both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two blisters in which the integrin expression was retained in the blister roof, despite loss of BPA. The other BMZ components were expressed on the blister floor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoimmune vesicles on the face and neck. A variant of Brunsting-Perry type localized bullous pemphigoid?

We report a case of blistering disease presenting a unique distribution of vesiculobullous lesions on the face and neck which is similar to Brunsting-Perry type of localized bullous pemphigoid (BP). Histopathology of a lesional skin biopsy demonstrated a subepidermal blister. Direct immunofluorescence demonstrated a strong linear deposition of IgG and IgA to the basement membrane zone, and a faint staining for C3. However, circulating antibodies were not detected by indirect immunofluorescence and immunoblotting. And the patient did not develop atrophic scars and was a relatively young woman. This case might be a variant of Brunsting-Perry type of localized BP or localized epidermolysis bullosa acquisita, presenting the clinical heterogeneity of subepidermal blistering diseases.     

Pemphigoid with antibodies to laminin γ1, BP180 and BP230, associated with psoriasis vulgaris: Successful disease control with cyclosporin

Both anti‐laminin γ1 pemphigoid and bullous pemphigoid are autoimmune subepidermal blistering diseases. The former is rare and characterized by autoantibodies to laminin γ1, a 200‐kDa dermal protein, while the latter is common among the elderly and characterized by autoantibodies to BP180 and BP230, both of which are hemidesmosomal proteins. We experienced a 69‐year‐old Japanese male patient with blister formation secondary to erythrodermic psoriasis, which was successfully treated with cyclosporin. The histopathology of erythema corresponded with psoriasis and that of a blistering lesion showed infiltration of neutrophils and eosinophils in and around the subepidermal blisters. Patient immunoglobulin G antibodies labeled both the epidermal and dermal sides of 1 mol/L NaCl‐split human skin by indirect immunofluorescent microscopy and recognized laminin γ1, BP180 and BP230 by immunoblotting. To the best of our knowledge, this is the first report of coexistence of psoriasis and atypical pemphigoid with these three autoantibodies.     

Characterization of the anti-BP180 autoantibody reactivity profile and epitope mapping in bullous pemphigoid patients

Bullous pemphigoid is a subepidermal bullous disease of skin and mucosae associated with autoantibodies to BP180. To characterize the humoral response to BP180, we generated a random BP180 epitope library displayed on lambda bacteriophage. After validation of the library by epitope mapping of three BP180-specific monoclonal antibodies, 15 novel or known BP180 epitopes were identified using 10 bullous pemphigoid serum samples. Fifty-seven bullous pemphigoid and 81 control sera were then assayed against the selected epitopes. Thirty-one out of 57 (54%) bullous pemphigoid sera reacted with at least an additional antigenic site other than the NC16A, within the extracellular (37%) and intracellular (28%) domains of BP180. In addition, the reactivity with extracellular epitopes of BP180 contained within the residue stretches 508-541 and 1331-1404 appeared to be related to the presence of both skin and mucosal involvement. Finally, a preliminary analysis of the epitope pattern in the disease course indicated that bullous pemphigoid patients exhibit a specific reactivity pattern, and that binding to intracellular epitopes of BP180, in addition to NC16A, may be detectable at an early clinical stage. Our findings provide novel insights into the pathophysiology of bullous pemphigoid and show the potential of the utilized approach as a tool for a rapid diagnosis of bullous pemphigoid patients and their management.     

Autoimmune subepidermal blistering diseases in Uganda: correlation of autoantibody class with age of patients

BACKGROUND: No data are available on the incidence and immunoreactivity of autoimmune subepidermal blistering skin diseases in East Africa. METHODS: All patients with frank blisters/erosions on the skin and/or mucous membranes that attended the Department of Dermatology at Mbarara University, Uganda, from May 2000 to June 2002, were investigated. The diagnosis was based on the clinical presentation and on the presence of circulating autoantibodies detected by indirect immunofluorescence microscopy on 1 m NaCl-split human skin and by Western blotting of recombinant and cell-derived forms of BP180, BP230, and type VII collagen. RESULTS: Twenty-two patients with autoimmune subepidermal blistering skin disorders were identified, including nine with bullous pemphigoid (41%), four with linear immunoglobulin A (IgA) disease (18%), three with mucous membrane pemphigoid (14%), two with linear IgG/IgA bullous dermatosis (9%), and one each with cicatricial pemphigoid and epidermolysis bullosa acquisita (5%). In addition, two patients with immunoreactivity to both the epidermal and dermal side of salt-split skin by indirect immunofluorescence microscopy, who were unreactive to type VII collagen, were provisionally diagnosed as "mixed pemphigoid" (9%). In patients with subepidermal blistering diseases, IgG reactivity correlated significantly with old age, whereas younger patients preferentially developed IgA autoantibodies (P = 0.024). CONCLUSIONS: The age of patients with autoimmune subepidermal blistering diseases appears to influence the immunoglobulin class of autoantibodies. The high frequency of IgA autoantibodies in Ugandan patients may be explained by the age distribution of the Ugandan population.     

IgG autoantibodies from a lichen planus pemphigoides patient recognize the NC16A domain of the bullous pemphigoid antigen 180

Lichen planus pemphigoides (LPP) most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We describe the case of a 49-year-old patient with features characteristic of LPP. Direct immunofluorescence microscopy studies demonstrated linear deposits of C3 along the cutaneous basement membrane, while circulating IgG autoantibodies directed against the epidermal side of skin separated by 1 M NaCl were detected. The patient's serum contained IgG autoantibodies immunoblotting a recombinant form of bullous pemphigoid antigen 180 (BP180), but not the COOH-terminus of BP230. By using deletion mutants, it was found that IgG reactivity was restricted to the NC16A domain of BP180, the region harboring the major antigenic sites targeted by IgG autoantibodies from patients with the bullous pemphigoid group of disorders. Our findings provide support to the idea that a subset of patients with LPP have a distinct form of bullous pemphigoid associated with lichen planus.     

Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain

Bullous pemphigoid, the most common autoimmune subepidermal bullous disorder, is associated with autoantibodies targeting antigenic sites clustered within the extracellular domain of BP180. To investigate epitope and subclass specificity of autoantibodies in bullous pemphigoid, we developed an enzyme-linked immunosorbent assay utilizing baculovirus-expressed recombinant forms of the NH2- and COOH-terminal regions of the extracellular domain of BP180 and examined sera obtained from patients with active bullous pemphigoid (n=116) and controls (n=100). Ninety-three (80%) and 54 (47%) of the 116 bullous pemphigoid sera recognized the NH2- and COOH-terminal regions, respectively, of the extracellular domain of BP180. Detailed analysis demonstrates that (i) this novel enzyme-linked immunosorbent assay is highly specific (98%) and sensitive (93%) as 108 of 116 bullous pemphigoid sera reacted with at least one of the baculovirus-derived recombinants, (ii) in active bullous pemphigoid, autoantibodies against the NH2-terminus of the extracellular domain of BP180 were predominantly of the IgG1 class, whereas a dual IgG1 and IgG4 response to this region was related to a more severe skin involvement, (iii) autoreactivity against both the NH2- and COOH-terminal regions was more frequently detected in patients with mucosal lesions, and (iv) levels of IgG (and IgG1) against the NH2-terminal, but not against the COOH-terminal portion of the extracellular domain of BP180, reflected disease severity indicating that autoantibodies against the NH2-terminus are critical in the pathogenesis of bullous pemphigoid. In conclusion, this novel enzyme-linked immunosorbent assay represents a highly sensitive and specific assay for rapid diagnosis of bullous pemphigoid and related disorders and may provide predictive parameters for the management of bullous pemphigoid patients.     

Autoantibodies to bullous pemphigoid antigen 180 induce dermal-epidermal separation in cryosections of human skin

Bullous pemphigoid is a subepidermal autoimmune blistering disease associated with autoantibodies to the hemidesmosomal bullous pemphigoid antigens 180 and 230. Most sera from bullous pemphigoid patients recognize epitopes within the N-terminal NC16A portion of the bullous pemphigoid 180 ectodomain. Using cryosections of human skin, patients' sera were shown to generate dermal-epidermal separation when coincubated with leukocytes and complement from healthy volunteers; however, the specificity of pathogenic autoantibodies in bullous pemphigoid patients has not yet been elucidated. In this study, by the use of a modified version of the cryosection model, we show that sera from all of 13 bullous pemphigoid patients and from two rabbits, immunized against bullous pemphigoid 180 NC16A, induced dermal-epidermal separation. This finding was confirmed with the use of IgG purified from patients' sera, whereas sera and purified IgG from healthy controls were not pathogenic. The induction of subepidermal splits in this experimental model was shown to be dependent on the presence of neutrophils, but not complement. Interestingly, patients' autoantibodies affinity purified against a recombinant form of bullous pemphigoid 180 NC16A retained their blister-inducing capacity, whereas patients' IgG depleted of reactivity to NC16A lost this ability. F(ab')2 fragments of antibodies specific to NC16A, lacking the Fc portion, did not induce splits. In addition, patients' autoantibodies purified against a recombinant fragment of the C-terminus of bullous pemphigoid 180 as well as rabbit antibodies to the intracellular portion of bullous pemphigoid 180 and to bullous pemphigoid 230 did not cause dermal-epidermal separation. Our in vitro results support the idea that autoantibodies to bullous pemphigoid 180 from patients with bullous pemphigoid are of pathogenic relevance.     

Increased expression of eotaxin and its specific receptor CCR3 in bullous pemphigoid.

Several skin infiltrating inflammatory cells, such as eosinophils, neutrophils and activated T lymphocytes, are involved in bullous pemphigoid (BP) blister formation. The presence of CD4+ T cells able to produce IL-4 and IL-5 suggests Th2 involvement in the disease. The role of eotaxin in the recruitment of eosinophils into inflammatory sites has been recently described and the specific eotaxin receptor, CCR3, has been documented to be expressed on eosinophils, basophils, and Th2 cells. In this study, we analyzed by immunohistochemistry the expression of both eotaxin and CCR3 in lesional skin from patients with active BP (n = 10) and control subjects affected with pemphigus vulgaris (PV) (n = 3); furthermore eotaxin concentration in BP sera and blister fluids was also evaluated by enzyme-linked immunosorbent assay (ELISA), in comparison to sera from PV and normal donors (n = 10) and to suction blisters from 3 healthy volunteers. A strong immunostaining for eotaxin and CCR3 in BP skin specimens in lesional and, to a lesser extent, in perilesional skin was observed. CCR3 expression was documented on both eosinophils and T cells infiltrating skin lesions. Eotaxin serum levels were significantly higher in BP patients when compared to healthy donors (p = 0.003) and PV patients (p = 0.01). The highest eotaxin concentration was detected in BP blister fluids, in respect to both corresponding BP sera and blister fluids from normal donors (p = 0.003). These results account for the role of eotaxin in the recruitment of activated cells at inflammatory sites during BP and the expression of CCR3 on infiltrating T lymphocytes further supports the involvement of Th2 cells in the pathogenesis of BP.     

Lichen planus pemphigoides: clinical and immunofluorescent findings in four cases

During the last 5 years we examined four black male patients who had features of both lichen planus (LP) and bullous pemphigoid (BP). The clinical disorder included classical lesions of LP along with bullae that developed subsequently and arose on both lesional and nonlesional skin. Histologic findings correlated well with the type of lesion on which biopsy was done, as did the immunofluorescent findings. All patients had features of both LP and BP by direct immunofluorescence and of BP by indirect immunofluorescence of serum and blister fluid.     

Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of patients with bullous pemphigoid: the first survey in Greece

Bullous pemphigoid (BP) is an acquired bullous disease with an increasing prevalence among elderly people worldwide, including in Greece. Blister formation in most patients with BP is caused by autoantibodies against structural components of the basement membrane zone of the skin, predominantly BP180NC16a and BP230 antigens on the hemidesmosome adhesion complex. Routine diagnostic methods such as histological examination and direct and indirect immunofluorescence are combined to determine diagnosis. In this study, an ELISA was used to measure levels of both anti-BP180NC16A and anti-BP230 autoantibodies in the blister fluid of 13 patients with newly diagnosed BP, before starting treatment. The aim of the study was to evaluate this method as a diagnostic tool in BP. Our results indicate that blister-fluid examination by ELISA can be a useful tool to diagnose bullous pemphigoid, especially in elderly patients who refuse biopsy or have poor venous access.