Immunological aspects of immunodeficiency diseases part 97

The cleavage  of pro-IL-1b to its active product IL-1 by the action of caspase-1 (interleukin converting enzyme) is a key event in the generation of an acute inflammatory response. Activated caspase-1, intern, is generated from pro-caspase-1 by the action  of activated forms of two cytosolic proteins called pyrin and cryopyrin, acting via adaptor proteins. The best-characterized adaptor protein is called ASC (apoptosis-associated speclike protein with a caspase recruitment domain). Mutations of components of this system (also called an inflammasome) give rise to most auto-inflammatory syndromes characterized to date. The nett effect of all these mutations is to impair homeostasis of the pro-inflammatory cytokine IL-1, NFκB activation, and cellular apoptosis. Impaired cellular apoptosis leads to the persistence of activated leucocytes that would otherwise undergo apoptosis, leading to the resolution of inflammation. Collectively, these abnormalities permit the inappropriate amplification and persistence of  inflammatory responses leading to the clinical features of the autoinflammatory syndromes.