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

BACKGROUND: IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical and immunological findings in 104 cases of paraneoplastic pemphigus.

BACKGROUND: Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported. OBJECTIVES: To analyse the clinical and immunological findings in a large cohort of patients with PNP. METHODS: This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assays (ELISAs) were analysed. RESULTS: The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty-two (60%) of 53 patients had antibodies to alpha-2-macroglobulin-like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans. CONCLUSIONS: We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.

A case of lichen planus pemphigoides with autoantibodies to the NC16a and C-terminal domains of BP180 and to desmoglein-1.

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease that occurs in association with lichen planus (LP). This report describes a 59-year-old Japanese female patient with LPP. The patient first showed LP lesions on her hands, and subsequently developed bullae on her extremities and erosions of the oral mucosa. The patient's serum was positive for IgG autoantibodies against the BP180 NC16a domain, the BP180 C-terminal domain and desmoglein-1. However, a serum sampled one and a half years before the diagnosis of LPP was negative for autoantibodies against BP180 NC16a and BP180 C-terminal domains. These findings strongly suggest that the damage to the basal cells in the LP lesions exposed a sequestered antigen or formed neoantigens, leading to the production of pathogenic autoantibodies for LPP. Most of the previous cases of LPP have produced autoantibodies to the NC16a domain of BP180. This is the first case in which autoantibodies to the C-terminal domain of BP180 were detected. The oral mucosal symptoms in this case may have been caused by autoantibodies to the BP180 C-terminal domain.