Clues of HLAs, metabolic SNPs, and epigenetic factors in T cell-mediated drug hypersensitivity reactions
Rasol Molatefi,
Sedighe Talebi,
Azam Samei,
Neda Roshanravan,
Shirin Manshouri,
Baran Hashemi,
Vahid Ghobadi Dana,
Erfan Mosharkesh,
Mohammad Ali Bahar,
Sholeh Khajoei,
Farhad Seif
Affiliations
Rasol Molatefi
Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
Sedighe Talebi
Department of Traditional Medicine, School of Persian Medicine, Shahed University, Tehran, Iran
Azam Samei
Department of Laboratory Sciences, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
Neda Roshanravan
Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Shirin Manshouri
Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Baran Hashemi
Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Vahid Ghobadi Dana
Department of Immunology and Allergy, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran
Erfan Mosharkesh
Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
Mohammad Ali Bahar
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Sholeh Khajoei
Clinical Research Development Center, Imam Khomeini Hospital, Jiroft University of Medical Sciences, Jiroft, Iran; Corresponding author. Enghelab St., Aboureyhan St., Tehran, Iran.
Farhad Seif
Department of Photodynamic Therapy, Medical Laser Research Center, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran; Department of Immunology and Allergy, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran; Corresponding author. Imam Khomeini Hospital, Jiroft, Iran.
Drug hypersensitivities are common reactions due to immunologic responses. They are of utmost importance because they may generate severe and fatal outcomes. Some drugs may cause Adverse Drug Reactions (ADRs), such as drug hypersensitivity reactions (DHRs), which can occur due to the interaction of intact drugs or their metabolites with Human Leukocyte Antigens (HLAs) and T cell receptors (TCRs). This type develops over a period of 24–72 h after exposure and is classified as type IV of DHRs. Acute generalized exanthematic pustulosis (AGEP), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are types of Severe Cutaneous Adverse Reactions (SCARs). In this review, we aim to discuss the types of ADRs, the mechanisms involved in their development, and the role of immunogenetic factors, such as HLAs in type IV DHRs, single-nucleotide polymorphisms (SNPs), and some epigenetic modifications, e.g., DNA/histone methylation in a variety of genes and their promoters which may predispose subjects to DHRs. In conclusion, development of promising novel in vitro or in vivo diagnostic and prognostic markers is essential for identifying susceptible subjects or providing treatment protocols to work up patients with drug allergies as personalized medicine.
