RT Journal Article
SR Electronic
T1 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 46ra62
OP 46ra62
DO 10.1126/scitranslmed.3001116
VO 2
IS 46
A1 Picard, Damien
A1 Janela, Baptiste
A1 Descamps, Vincent
A1 D’Incan, Michel
A1 Courville, Philippe
A1 Jacquot, Serge
A1 Rogez, Sylvie
A1 Mardivirin, Laurent
A1 Moins-Teisserenc, Hélène
A1 Toubert, Antoine
A1 Benichou, Jacques
A1 Joly, Pascal
A1 Musette, Philippe
YR 2010
UL http://stm.sciencemag.org/content/2/46/46ra62.abstract
AB Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug-induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4+ and CD8+ and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8+ T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor–α and interferon-γ. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8+ T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8+ T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients’ EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8+ T lymphocytes, which are largely directed against herpes viruses such as EBV.