Autoinflammatory Disorders – Primary Immunodeficiency

00:01 There are a number of conditions in which there is uncontrolled inflammatory responses that are caused by particular gene defects.

00:13 In fact there are more than 30 different autoinflammatory disorders that have been described.

00:19 Some of these are monogenic, others are polygenic.

00:24 There are episodes of apparently unprovoked inflammation, with fever, rashes, joint and muscle aches and abdominal and chest pain.

00:34 Importantly, there is dysregulated expression or control of pro-inflammatory cytokines.

00:43 One of the better characterized autoinflammatory disorders is familial Mediterranean fever, in which pyrin mutations in this inflammasome regulator that’s expressed in neutrophils and monocytes results in the inflammasomes generating active caspase-1 which converts pro-IL-1β into active IL-1β.

01:10 And there’s excessive production of this pro-inflammatory cytokine.

01:15 In the cryopyrin-associated periodic syndrome or CAPS, there are mutations in NLRP3 which is another inflammasome component.

01:28 Deficiency of the interleukin-1 receptor antagonist or DIRA as the disease is known, is due to mutations in this particular regulator of IL-1 activity.

01:44 And therefore there is a uncontrolled IL-1β activity, and IL-1β is another pro-inflammatory cytokine.

01:53 The TNF receptor-associated syndrome or TRAPS, results from mutations in the p55 component of the TNF receptor.

02:04 Hyper-IgD syndrome or HIDS, which is also called hyperimmunoglobulinemia D with periodic fever syndrome is due to mutations in the mevalonate kinase gene.

02:17 And indirectly leads to increased production of interleukin-1β.