Autoimmune Mechanism May Cause Drug-Induced Adverse Reactions

U.S. Food and Drug Administration (FDA) researchers have discovered a new mechanism for identifying and understanding drug-related autoimmune reactions. Specifically, they found that in certain at-risk patients, the anti-HIV drug Ziagen (abacavir) causes the immune system to “see” a patient’s own healthy tissues and proteins as a foreign invader. The effect is similar to what happens when the immune system recognizes a viral or bacterial protein during an infection. Abacavir is known to cause allergic reactions, which can range from mild skin reactions to severe allergic shock and even death, in certain at-risk patients.

Abacavir interacts with molecules in the immune system called human leukocyte antigens (HLAs), specifically HLA-B*5701, which help the body to distinguish “self” versus “foreign” proteins. The drug can cause HLA-B*5701 to present for the first time certain “self” proteins that the body has not seen before and mistakenly treats them as foreign, resulting in the body trying to destroy its own tissues. HLA-B*5701 is known to be a risk factor for serious reactions to abacavir.

This discovery will provide the FDA with new tools to analyze the safety of drugs that have the potential to cause severe allergic reactions. And, it will advance the FDA’s ability to approve therapies that are personalized for safety. The results also may give biopharmaceutical companies and other research organizations new methods to identify early in the development process drugs with the potential to cause severe adverse drug reactions. This may also serve as a model for future research to predict drug reactions in different populations of at-risk patients.