Other names: Deficiency of Interleukin-1 Receptor Antagonist; DIRA

Deficiency of Interleukin-1 Receptor Antagonist (DIRA) is a very rare, genetic, autoinflammatory disease caused by autosomal recessive mutations in the IL1RN gene.

The IL1RN gene produces the interleukin-1 receptor antagonist (IL-1Ra) protein, which plays a critical role in helping regulate the interleukin-1 (IL-1) signaling pathway. IL-1 is a powerful driver of inflammation and plays an important role in the body’s immune response. IL-1 pro-inflammatory signaling primarily occurs through IL-1α and IL-1β. IL-Ra competes with IL-1α and IL-1β, inhibiting pro-inflammatory signaling. In patients with DIRA, the deficiency of the IL-1Ra leads to unopposed action of IL-1α and IL-1β, resulting in life-threatening systemic inflammation with skin and bone involvement.

DIRA usually presents in newborns at birth or in the first few days of life, and the severe inflammatory reaction resembles an acute severe systemic infection, or infection of the bone. As DIRA can be life-threatening, early diagnosis and treatment is essential to prevent death multi-organ failure and death.

Treatments for DIRA include anakinra, an interleukin-1 receptor antagonist (IL-1Ra), and rilonacept, an interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) cytokine trap.

Drugs used to treat Interleukin-1 Receptor Antagonist Deficiency