Treg cells as potential therapeutic targets for bullous pemphigoid: A review.

Regulatory T cell subsets in bullous pemphigoid and dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid

A 230-kD Basic Protein Is the Major Bullous Pemphigoid Antigen

Detection of IgG Autoantibodies in the Sera of Patients with Bullous and Gestational Pemphigoid: ELISA Studies Utilizing a Baculovirus-Encoded Form of Bullous Pemphigoid Antigen 2

Comparative Study of Bullous Pemphigoid Antigens Among Japanese, British, and U.S. Patients Indicates Similar Antigen Profiles with the 170-kD Antigen Present both in the Basement Membrane and on the Keratinocyte Cell Membrane

Heterogeneity of Pemphigoid Antigens

Previous reports have shown that indirect immunofluorescence (IIF) performed on sodium chloride-split skin (SSS) is helpful to differentiate epidermolysis bullosa acquisita (EBA) from bullous pemphigoid (BP). Antibodies of BP may bind to the epidermal side of SSS, while antibodies of EBA bind to the dermal side. To determine the accuracy of IIF-SSS in the differential diagnosis of EBA and BP utilizing immunoblotting (IB) analysis. Sera from 78 patients, diagnosed with BP by clinical features, histopathology, and direct immunofluorescence (DIF), were assayed using IIF-SSS and IB. Of the 43 serum samples with an epidermal reaction to IIF-SSS assay, 42 were recognized with BP antigens (180 kDa or 230 kDa). Of the 11 serum samples with a dermal reaction pattern, 7 were recognized with the 290 kDa antigen of EBA and 3 with sera bound BP antigens. Seven serum samples with epidermal and dermal combined staining, of which 5 of them reacted with BP antigens, 1 reacted with both BP and EBA antigens. One serum sample from each group showed a negative result by IB. Approximately 9.0% (7/78) of patients diagnosed with BP using regular methods were actually EBA. Epidermal reaction using the IIF-SSS assay highly correlated with the diagnosis of BP. However, dermal reactions correlated poorly with EBA, with some serum samples from BP patients binding to dermal-side antigens. In both epidermal and dermal stained sera using IIF-SSS, there was a possibility of BP and EBA. Differential diagnosis should be confirmed using IB, especially in cases of dermal and double staining patterns assayed using IIF-SSS.

Regional Variation in the Expression of Bullous Pemphigoid Antigen and Location of Lesions in Bullous Pemphigoid

A case of bullous pemphigoid provoked by doxycycline-induced phototoxicity

Characterization of bullous pemphigoid antigen: A unique basement membrane protein of stratified squamous epithelia

Bullous Pemphigoid Antigen: cDNA Cloning, Cellular Expression, and Evidence for Polymorphism of the Human Gene

The bullous pemphigoid (BP) antigen(s) is a normal component of the base-ment membrane zone (BMZ) of skin and other stratified squamous epithelia and is defined by its interaction with autoantibodies present in the sera of patients with BP, as demonstrated by immunofluorescent (IF) techniques. The precise physiological function and the biochemical characterization of the BP antigen remain unclear. BP autoantibodies have been recently shown to be pathogenic in vitro and in vivo. They promote neutrophil recruitment to the BMZ by com-plement activation and reproduce subepithelial vesiculation, the hallmark of the human disease. As a consequence of these findings, the characterization of the BP antigen(s) is crucial in studies dealing with pathogenetic mechanisms operating in the disease.The localization of the BP antigen has been studied previously, using both immunofluorescence (W) and immunoelectron microscopic techniques (immuno-EM). Using standard indirect IF, employing sera from patients with BP, it is established that BP antibodies bind the BMZ, producing a linear pattern of fluo-rescence on vertical sections of squamous epithelium. Direct and indirect im-muno-EM using immunoperoxidase techniques have shown that BP autoanti-bodies in vitro are deposited within the lamina lucida of the BMZ, in close apposition to the basal cell plasma membrane. This would imply that the BP antigen is located there as well.We have made a series of experimental observations performed both on intact epidermis and on basal cell suspensions, which show that, contrary to previous assumptions, the majority of the BP antigen is intracellular, closely associated with the basal cell hemidesmosome and only a small portion of it is extracellular in the lamina lucida. In view of these results we must reconsider our concepts of the in situ localization of the BP antigen(s).Previous immunoblotting and immunoprecipitation studies identified only one antigen (a doublet with an estimated MW of 220 kD to 240 kD). In a recent study we report that a group of 28 BP sera recognize up to 5 different poly-peptide chains in epidermal extracts by immunoblotting procedures, with individual sera recognizing different sets of these polypeptide chains. Therefore, different BP patients may have various sets of autoantibodies that are defined by the antigens with which they react. It will now be essential to determine the relationship of the 5 proteins reactive with BP sera by immunoblotting in epidermal extracts with the structural components of the basal cell hemides-mosome.

Production of Rabbit Antibodies Against Carboxy-Terminal Epitopes Encoded by Bullous Pemphigoid cDNA

The major bullous pemphigoid (BP) antigen is a 220-240-kDa polypeptide, although some BP sera recognize bands of 180-200 kDa or lower molecular weight. We have investigated to what extent this heterogeneity of the target antigen accounts for the clinical diversity of BP. Immunoblotting studies against extracts of salt-separated epidermis were performed on sera from 39 patients with BP. The blotting patters obtained were correlated with the clinical findings, with particular reference to prodromal itching, lesion morphology and severity, mucosal involvement, presence of milia, dapsone responsiveness and disease duration. The results confirm that the major BP antigen is a 220-kDa polypeptide, and that the 180-kDa polypeptide is a second and sometimes the sole BP antigen identified in immunoblots. Rarely, multiple bands of lower molecular weight were found. There was no correlation between the pattern of BP antigens detected in immunoblots and the clinical presentation and course of BP. There was considerable clinical diversity even among the nine patients showing specificity for a single 220-kDa target antigen. Although two patients with a single 180-kDa antigen specificity had a disease of unusually long duration, factors other than antigen specificity must determine the clinical expression of BP.

Epidermolysis Bullosa: Variability of Expression of Cicatricial Pemphigoid, Bullous Pemphigoid, and Epidermolysis Bullosa Acquisita Antigens in Clinically Uninvolved Skin

358 Treg dysfunction leads to spontaneous production of autoantibodies to bullous pemphigoid antigens in mice