Autoinflammatory diseases constitute a group of
genetic disorders whose main clinical features are recurrent episodes of inflammatory lesions that can affect the skin, joints, bones, eyes, gastrointestinal tract and nervous system, in association with signs of systemic
inflammation. Example of these disorders is
familial Mediterranean fever (FMF). FMF is an autosomal recessive disease characterized by recurrent episodes of
fever and
inflammation affecting serosal surfaces, joints and skin. The gene of FMF is expressed in granulocytes, monocytes, dendritic cells and serosal and sinovial fibroblasts, which result in formation of
pyrin. A large percentage of FMF-associated
pyrin mutations reside in C-terminal B30.2 domain.
Pyrin normally suppresses IL-1β, but when mutated in case of FMF, it does not. Inhibition of the interaction between
pyrin and caspase-1 leads to an increase in caspase-1 activity and subsequent increase in IL-1β secretion. The interleukin-1-receptor antagonist binds to the
interleukin-1 receptor, thereby blocking access of
interleukin-1 to the receptor. The outcome of an inflammatory process is likely to be affected by the relative amounts of
interleukin-1 and interleukin-1-receptor antagonist.