Some 15 years ago, the term autoinflammatory syndrome has been coined to delineate a group of disorders in which patients suffer from recurrent or chronic inflammation without an obvious exogenous trigger. In earlier days, these syndromes were described as periodic or episodic fevers; the most prominent among these are Familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), Hyper-IgD syndrome (HIDS) and Cryopyrin-associated periodic syndrome (CAPS). Today, some 15 different autoinflammatory disorders have been recognised as autoinflammatory syndromes. Elucidation of the genetic background, using modern genetic techniques, has taught a lot about the inflammatory pathways in many these disorders. Baseline activation of inflammasomes (hetero- and homo-multimeric protein complexes that trigger cytokine activation) appears to play a role in many of these disorders. Among the cytokines that are activated, especially interleukin-1beta (IL-1beta) stands out. This is further corroborated by a beneficial effect of therapeutic interventions directed towards IL-1beta, using either recombinant IL-1 receptor antagonist (anakinra), soluble decoy receptor construct (rilonacept) or neutralising monoclonal antibody against IL-1beta. We are now at a stage where it is realised that not all autoinflammatory syndromes respond in the same way to IL-1 blockade, pointing to the complexity of the cytokine network and the role of pro-inflammatory cytokines other than IL-1beta.
Originally, a sharp distinction was made between autoinflammatory syndromes and autoimmune disorders. In the former, autoreactive T- and/or B-lymphocytes, which are a hallmark of autoimmunity, were thought to be absent. By the recognition of syndromes with autoinflammatory and autoimmune traits, this distinction has become less strict. This also implies that not all autoinflammatory syndromes are pure disorders of an overactive innate immune system.
Disclosure of Interest None declared
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