There are a number of conditions in which there is uncontrolled
inflammatory responses that are
caused by particular gene defects.
In fact there are more than 30 different
autoinflammatory disorders that have been described.
Some of these are monogenic,
others are polygenic.
There are episodes of apparently unprovoked inflammation, with
fever, rashes, joint and muscle
aches and abdominal and chest pain.
Importantly, there is dysregulated expression
or control of pro-inflammatory cytokines.
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.
And there’s excessive production
of this pro-inflammatory cytokine.
In the cryopyrin-associated periodic syndrome or CAPS, there
are mutations in NLRP3 which is another inflammasome component.
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.
And therefore there is a uncontrolled IL-1β activity,
and IL-1β is another pro-inflammatory cytokine.
The TNF receptor-associated syndrome or TRAPS, results
from mutations in the p55 component of the TNF receptor.
Hyper-IgD syndrome or HIDS, which is
also called hyperimmunoglobulinemia D
with periodic fever syndrome is due to
mutations in the mevalonate kinase gene.
And indirectly leads to increased
production of interleukin-1β.