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Castelnovo ne'Monti, Italy

Di Zenzo G.,Molecular and Cell Biology Laboratory | Carrozzo M.,Northumbria University | Chan L.,Illinois College
Oral Diseases | Year: 2014

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune subepithelial blistering diseases affecting primarily mucous membranes showing marked degree of clinical and immunological variability. We investigated four controversial topics: (i) Does oral pemphigoid (OP) really exist as a separate entity? (ii) Is mucous membrane pemphigoid curable? (iii) What is the best therapeutic option for MMP? (iv) Does exclusive oral IgA dermatitis exist as a distinct entity from MMP? Results from extensive literature searches suggested that (i) it is still unclear whether patients with OP could be considered as a distinct subset of MMP with specific clinical and immunological features; (ii) it is uncertain whether treatment regimens that get MMP under control can be eliminated to allow patients to be in drug-free remission or they should be continuously administered in some capacities; (iii) there is a concerning paucity of good-quality trials on MMP and available recommendations are solely based on generally small patients' cohorts or case series. Some of the 2002 consensus experts' opinions should be possibly updated, particularly regarding the safety of sulfa drugs; (iv) we did not find any strong evidence to support an exclusive oral (and perhaps also mucosal) form of LAD as a separate entity. © 2013 John Wiley & Sons A/S. Source

Khudhur A.S.,Northumbria University | Di Zenzo G.,Molecular and Cell Biology Laboratory | Carrozzo M.,Northumbria University
Expert Review of Molecular Diagnostics | Year: 2014

The concept of lichenoid tissue reaction/interface dermatitis was introduced in dermatology to define a number of diverse inflammatory skin diseases linked together by the presence of common histopathological features. Similarly to the skin, the oral mucosa is affected by a variety of oral lichenoid lesions. Oral LTRs (OLTRs) include: oral lichen planus; oral lichenoid contact lesion; oral lichenoid drug reaction; oral lichenoid lesions of graft-versus-host disease; oral discoid lupus erythematosus; oral lesions of systemic lupus erythematosus; erythema multiforme; paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome; chronic ulcerative stomatitis and lichen planus pemphigoid. Traditionally, diagnosis of OLTRs relies on clinical and histological correlation but in several instances this approach fails to provide a reliable diagnosis. Inclusion of molecular techniques may refine our ability to differentiate OLTRs. © 2014 Informa UK, Ltd. Source

Di Zenzo G.,Molecular and Cell Biology Laboratory | Thoma-Uszynski S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Calabresi V.,Molecular and Cell Biology Laboratory | Fontao L.,University of Geneva | And 7 more authors.
Journal of Investigative Dermatology | Year: 2011

Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period. Epitope-spreading (ES) events were detected in 17 of 35 BP patients (49%). They preferentially occurred in an early stage of the disease and were significantly related to disease severity at diagnosis. Moreover, in three patients, spreading of IgG reactivity to intracellular epitopes of BP180 and BP230 was preceded by recognition of the BP180 ectodomain. Finally, IgG reactivity with extracellular epitopes of BP180 and intracellular epitopes of BP230 correlated with the severity of BP in disease course. These findings support the idea that IgG recognition of the BP180 ectodomain is an early and crucial event in BP disease, followed by variable intra- and intermolecular ES events, which likely shape the individual course of BP. © 2011 The Society for Investigative Dermatology. Source

Pomponi D.,Center for Molecular Allergology | Di Zenzo G.,Molecular and Cell Biology Laboratory | Zennaro D.,Center for Molecular Allergology | Calabresi V.,Molecular and Cell Biology Laboratory | And 5 more authors.
British Journal of Dermatology | Year: 2013

Background Bullous pemphigoid (BP) is an autoimmune skin disease in which patient autoantibodies react with BP180 and BP230 proteins. In addition to IgG, IgE has been shown to play a role in the disease. Objectives To evaluate the feasibility of detecting IgE and IgG against the immunodominant BP180 NC16A domain (BP180) using a microarray system. Methods BP180 was immobilized on an experimental version of the ISAC® microarray (Exp96). The BP study group and the controls were all tested on the commercial ISAC 103 version and on the Exp96. IgG and IgE were measured in a single run. BP180 IgG and IgE results were compared with those using an enzyme-linked immunosorbent assay (ELISA). Results All results obtained using the IgG ELISA on the 31 patients with BP were replicated with the ISAC IgG. Five of eight BP sera tested by ELISA showed similar results with ISAC IgE. Twenty-nine (94%) and 19 (61%) of the 31 patients with BP were IgG and IgE positive to BP180, respectively, whereas four (3%) and six (4%) of 138 normal donors were IgG and IgE positive, respectively. Interestingly, the levels of IgG against BP180 detected using the ISAC system were related to the disease severity. Patients with BP showed a peculiar profile of IgE recognition toward some groups of allergens, which was absent in a group of allergic individuals. A significant, higher prevalence of hen's egg recognition was observed in patients with BP who had specific IgE to BP180. Conclusions The present preliminary study indicates that the ISAC microarray system is suitable for detecting IgG and IgE autoantibodies in patients with BP. Notably, this system allows the assessment of IgE and IgG autoantibodies at the same time, could be employed for the detection of autoantibodies to other autoantigens, and allows profiling for specific IgE to allergens. What's already known about this topic? Bullous pemphigoid (BP) is a severe autoimmune blistering disease. IgG and IgE autoantibodies to skin BP180 and BP230 autoantigens are detected by enzyme-linked immunosorbent assay (ELISA) in patients with BP. IgE seem to play a role in a subset of patients with more severe disease. What does this study add? IgG and IgE autoantibodies in BP sera were detected using the immunodominant portion of BP180 immobilized on a microarray along with allergenic molecules, with almost overlapping results compared with ELISAs. Specific IgE allergen profiles differ in patients with BP and control groups. Specific BP180 IgG and IgE are rarely detected in an allergic population. © 2012 The Authors. BJD © 2012 British Association of Dermatologists. Source

Di Zenzo G.,Molecular and Cell Biology Laboratory | della Torre R.,University Hospital Inselspital | Zambruno G.,Molecular and Cell Biology Laboratory | Borradori L.,University Hospital Inselspital
Clinics in Dermatology | Year: 2012

Bullous pemphigoid (BP) constitutes the most frequent autoimmune subepidermal blistering disease. It is associated with autoantibodies directed against the BP antigens 180 (BP180, BPAG2) and BP230 (BPAG1-e). The pathogenicity of anti-BP180 antibodies has been convincingly demonstrated in animal models. The clinical features of BP are extremely polymorphous. The diagnosis of BP critically relies on immunopathologic findings. The recent development of novel enzyme-linked immunosorbent assays has allowed the detection of circulating autoantibodies with relatively high sensitivity and specificity. Although potent topical steroids have emerged in the past decade as first-line treatment of BP, management of the disease may be challenging. © 2012 Elsevier Inc. Source

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