Fig. 2

Cryopyrin-associated periodic fever syndrome (CAPS), TNF receptor-associated periodic syndrome (TRAPS), and autoinflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) are related to NLRP3 inflammasome. Gain-of-function mutations of NLRP3 (e.g., R260W) leads to prolonged activation of NLRP3 inflammasome. Autoinflammatory syndrome caused by the gain of function of NLRP1, NLRP12, or other NLRP mutations is thought to be basically caused by the same mechanisms. Mutated TNFRSF1A (TNFR) in patients with TRAPS is misfolded and accumulated in the endoplasmic reticulum (ER), causing ER stress and increased generation of mitochondrial reactive oxygen species (ROS) that activates the NLRP3 inflammasome. PLCγ2 mutation in patients with APLAID (e.g., S707Y) leads to calcium influx from the ER and increased cytoplasmic Ca2+ levels promote activation of NLRP3 inflammasome