Eosinophil localization to the basement membrane zone is autoantibody- and complement-dependent in a human cryosection model of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by antibodies (IgG and IgE) targeting cell-substrate adhesion proteins. A variety of BP models suggest that autoantibody-dependent neutrophil degranulation is essential for blister formation. However, lesional biopsies reveal a predominance of eosinophils and few neutrophils. Our goal was to evaluate the role of antibodies and complement in eosinophil localization, degranulation and split formation at the dermo-epidermal junction (DEJ) utilizing a human skin cryosection model of BP paired with a human eosinophilic cell line, 15HL-60. Expression of receptors for IgG (FcγRII), IgE (FcεRI) and complement (CR1 and CR3) was confirmed on 15HL-60 cells using flow cytometry. 15HL-60 expression of granule protein [eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO)] mRNA and their degranulation in vitro was confirmed using RT-PCR and ELISA, respectively. For cryosection experiments, BP or control sera or IgG and IgE antibodies purified from BP sera were utilized in combination with 15HL-60 cells ± fresh complement. Both BP serum and fresh complement were required for localization of 15-HL60 cells to the DEJ. Interestingly, eosinophil localization to the DEJ was dependent on IgG, but not IgE, and complement. However, no subepidermal split was observed. Additionally, the 15HL-60 cells did not degranulate under any experimental conditions and direct application of cell lysate to cryosections did not result in a split. Our observation that eosinophil localization to the DEJ is dependent on IgG mediated complement fixation provides additional insight into the sequence of events during the development of BP lesions.

Health-related quality of life in patients with cutaneous T-cell lymphoma?

BACKGROUND: Little is currently known about health-related quality of life (HRQoL) of patients with cutaneous T-cell lymphoma (CTCL), a condition characterized by chronic, pruritic, visible lesions, features which may be uniquely influential. OBJECTIVE: The aim of this study was to establish baseline HRQoL data for patients with CTCL and identify its influencing factors. METHODS: Prospective, nonblinded survey design utilizing questionnaires including panels of QoL indices obtained from 105 patients with mycosis fungoides, Sezary syndrome, and CD30+ lymphoproliferative disorder. Chart review correlated QoL with year of disease onset/diagnosis, type/stage of disease, current/past therapies, and medical/psychiatric diagnoses. RESULTS: Psychiatric condition was significantly associated with symptoms (P < 0.01), emotions (P < 0.01), and functioning (P < 0.03) subscales along with overall composite measure (P < 0.01). High-grade systemic therapy (OR = 5.28) showed greater increase in odds of a lower health state than low grade (OR = 1.54). The number of medical comorbidities was significantly related to itching (P < 0.01). Increased age was a protective factor with respect to the emotions (P < 0.01), functioning (P < 0.01), and overall composite (P < 0.01) but not predictive of symptoms. Lower income was associated with higher bother on the symptoms subscale. CONCLUSIONS: HRQoL in CTCL appears related to a number of factors, including presence of a psychiatric condition, use of systemic (particularly high grade) therapy, number of medical comorbidities, and income.

Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, ß and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and ß-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.