Severe Delayed Drug Reactions : Role of Genetics and Viral Infections - 30/09/17

Doi : 10.1016/j.iac.2017.07.007

Rebecca Pavlos, PhD ^a,^{^{1
Co-first authors.}}, Katie D. White, MD, PhD ^b,^{^{1
Co-first authors.}}, Celestine Wanjalla, MD, PhD ^b, Simon A. Mallal, MBBS ^a,^b,^c, Elizabeth J. Phillips, MD ^a,^b,^c,^d,^⁎
^a Institute for Immunology and Infectious Diseases, Murdoch University, 6150 Murdoch, Western Australia, Australia
^b Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
^c Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
^d Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

^∗Corresponding author. 1161 21st Avenue South, A-2200 Medical Center North, Nashville, TN 37232-2582.1161 21st Avenue SouthA-2200 Medical Center NorthNashvilleTN37232-2582

Résumé

Adverse drug reactions (ADRs) are a significant source of patient morbidity and mortality and represent a major burden to health care systems and drug development. Up to 50% of such reactions are preventable. Although many ADRs can be predicted based on the on-target pharmacologic activity, ADRs arising from drug interactions with off-target receptors are recognized. Off-target ADRs include the immune-mediated ADRs (IM-ADRs) and pharmacologic drug effects. In this review, we discuss what is known about the immunogenetics and pathogenesis of IM-ADRs and the hypothesized role of heterologous immunity in the development of IM-ADRs.

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Keywords : Human leukocyte antigen, T-cell receptor, Adverse drug reaction, Pharmacogenomics, Human herpes virus, Drug reaction with eosinophilia and systemic symptoms, Steven Johnson syndrome, Toxic epidermal necrolysis