Checkpoints in the progression from hyperuricemia to the clinical manifestations of gout
Checkpoints in the progression from hyperuricemia to the clinical manifestations of gout
Factors controlling deposition of MSU crystals are not well understood. The acute flare results from production of mature interleukin 1 beta after activation of the NLRP3 inflammasome that occurs after ingestion of crystals by monocytes, which in humans, requires a second signal through TLRs. Flare resolution involves NETs, which bind MSU crystals. The NETs probably contribute to the formation of tophi.
ASC: apoptosis-associated speck-like protein containing a caspase recruitment domain;
LDL: low-density lipoprotein;
MAPK: mitogen-activated protein kinase;
MSU: monosodium urate;
NET: neutrophil extracellular trap;
NLRP3: NLR family pyrin domain containing 3;
TLR: toll-like receptor.
Reproduced from: Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet 2016; 388:2039. Illustration used with the permission of Elsevier Inc. All rights reserved.
