Characterization of skin blister fluids from children with Epstein–Barr virus‐associated lymphoproliferative disease

Abstract

Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids.

Coexpression of natural killer cell antigens by T-cell large granular lymphocytes in hydroa vacciniforme lymphoproliferative disorder and the involvement of Vδ1 + epithelial-type γδT cells

“…In our cHV patients, the CD3 + T cells also contained small percentages of CD16/CD56dim + cells. Although EBV presence was not directly confirmed on the surface of CD3 + T and γδT cells, most NK-like T cells may correspond to EBV + γδT cells, as EBER + cell counts and EBV DNA loads are increased in the γδT-cell fractions of cHV [ 6 , 19 , 25 , 26 ]. Furthermore, EBER + cells are primarily observed in the γδT-cell fraction using flow cytometric analysis on surface immunophenotypes and EBER 5 (Supplementary Fig.…”

A Suction Blister Protocol to Study Human T-cell Recall Responses <em>In Vivo</em>

“…The suction blister method has already been applied in many areas of medical research besides dermatology, either alone or in combination with a systemic or local skin challenge. Examples include studies of sepsis, Epstein-Barr virus-associated lymphoproliferative disease, diabetic neuropathy, glucocorticoid intake effects, and human trials testing therapeutic antibodies or models for T-cell-targeted therapies 10 34 35 36 37 38 .…”