Deficiency of the interleukin-1–receptor antagonist


Deficiency of the interleukin-1–receptor antagonist is an autosomal recessive, genetic autoinflammatory syndrome resulting from mutations in IL1RN, the gene encoding the interleukin 1 receptor antagonist. The mutations result in an abnormal protein that is not secreted, exposing the cells to unopposed interleukin 1 activity. This results in sterile multifocal osteomyelitis, periostitis, and pustulosis due to skin inflammation from birth.

Symptoms and signs

DIRA displays a constellation of serious symptoms which include respiratory distress, as well as the following:

Cause

Those affected with DIRA have inherited mutations in IL1RN, a gene that encodes a protein known as interleukin 1 receptor antagonist,
The cytogenetic location of IL1RN is 2q14.1, while its 2:113,099,364-113,134,015 are the genomic coordinates

Mechanism

The mechanism of deficiency of the interleukin-1–receptor antagonist affects the normal function of IL1RN gene. The protein produced by IL1RN gene prevents the normal activities of interleukin 1 and interleukin 1. Therefore, the pathophysiologic immune and inflammatory responses are nullified. Interleukin 1 receptor antagonist has a total of five alleles, of those the and are the most common as the other alleles are seen less than 5 percent.
IL-1RN binds to the same cell receptors as the inflammatory protein IL-1, and blocks its inflammatory actions. Without IL-1Ra, the body cannot control systemic inflammation that can be caused by IL-1.

Diagnosis

Those affected with deficiency of the interleukin-1–receptor antagonist can have diagnosis achieved via noting an increase of erythrocyte sedimentation rate, as well as the following:
In terms of treatment a 2013 review indicates that colchicine can be used for DIRA. Additionally there are several other management options such as anakinra, which blocks naturally occurring IL-1, this according to a 2016 pediatric textbook.