The investigators then evaluated the role of the NLRP3 inflammasome in patients with CAPS. To do this, they created recombinant oligomeric particles made of a p.D303N mutant form of NLRP3 that had been identified in patients with CAPS. They found that the particles of NLRP3(p.D303N) localized with extracellular ASC and were able to stimulate activation of caspase-1 extracellularly, and once phagocytosed by macrophages, intracellularly. Although macrophages were able to ingest recombinant NLRP3 (p.D303N) by phagocytosis, ingestion of the mutant inflammasome did not cause substantial cell death of macrophages.
The investigators went on to document the presence of extracellular inflammasome danger particles in the serum of patients with active CAPS. The oligomeric ASC particles were not found in the serum of patients with other inherited autoinflammatory diseases. (posted 11/7/14)
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
