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      Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System

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          Abstract

          Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted. In recent years, emerging studies have outlined the disease more clearly, though several important questions remain unresolved. In this review, we provide an overview of DRESS syndrome, including clinical presentations, histopathological features, pathomechanisms, and treatments.

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          Most cited references 133

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          Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects

          Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4 + and/or CD8 + T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average ∼10% of both the CD4 + and CD8 + memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8 + T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.
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            The nature of the principal type 1 interferon-producing cells in human blood.

            Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
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              Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries.

              Despite the great number of methods proposed, assessing the causal role of a drug in the occurrence of an adverse medical event remains one of the most controversial issues. Qualifying terms for criteria, such as "compatible", "suggestive" of "inconclusive", have never been strictly defined, leading to low reproducibility. Weights of the criteria are usually not adapted to the injured organ, decreasing the specificity of the method. In this paper, a new method for drug causality assessment is described. Contents and limits of the criteria have been defined by experts convened to organ-oriented international consensus meetings. Additional criteria have been introduced and weights attributed. The method was applied to reports of acute liver injuries. The reproducibility was tested by an independent team. The validity of this novel method is studied in the following paper, based on an original approach using reports with positive rechallenge as external standard.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 June 2017
                June 2017
                : 18
                : 6
                Affiliations
                Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; yungtsucho@ 123456gmail.com (Y.-T.C.); emilyyang0123@ 123456gmail.com (C.-W.Y.)
                Author notes
                [* ]Correspondence: chiayu@ 123456ntu.edu.tw ; Tel.: +886-2-2356-2141
                Article
                ijms-18-01243
                10.3390/ijms18061243
                5486066
                28598363
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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