Understanding HLA-associated drug reactions

About the study

Adverse drug reactions involving an abnormal immune system response, known as immunologically mediated adverse drug reactions (IM-ADRs), contribute disproportionally to drug-related diseases. T-cells, a white blood cell that helps the immune system fight germs and protect the body from infection, can contribute to drug reactions in a subset of IM-ADRs. These reactions are severe and life-threatening, causing acute skin diseases such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

The goal of the present study, Understanding HLA-associated Drug Reactions, led by Dr. Elizabeth Phillips, is to determine the mechanistic basis of HLA-associated drug hypersensitivity. HLA alleles help the immune system distinguish between the body’s proteins and proteins made by foreign invaders such as viruses and bacteria. At times, HLA alleles can react to the presence of drugs.  

Aims of the study

A specific aim of this study is to identify the primary T-cell receptor (TCR) used by T cells in drug-hypersensitive patients but not HLA risk allele-matched drug-tolerant controls. Another objective is to define the anti-viral T cells directed against chronically prevalent human herpes viruses present in drug-hypersensitive patients but not HLA risk allele matched drug-tolerant controls. Stored cell samples from HLA-B*57:01 positive abacavir hypersensitive and HLA-B*15:02 positive SJS/TEN patients will be analyzed to meet this objective. Finally, an additional aim is to identify anti-viral T cells in drug-hypersensitive patients that cross-recognize a drug in the context of the defined HLA risk allele.

Study results will inform strategies for predicting severe HLA-associated IM-ADRs and guide future drug development and design. 

Questions? 

Please email drugsafetyresearch@vumc.org for more information.